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THE  URINE  IN  HEALTH  AND  DISEASE,  AND 
URINARY  ANALYSIS. 


THE 

URINE  IN  HEALTH  AND  DISEASE, 


URINARY  ANALYSIS 

PHYSIOLOGICALLY  AND  PATHOLOGICALLY 
CONSIDERED. 


BY 

D.  CAMPBELL  BLACK,  M.D.,  L.R.C.S.  Edin., 
F.F.P.  &  S.  Glas., 

PROFESSOR  OF  PHYSIOLOGY  IN  ANDERSON'S  COLLEGE  MEDICAL  SCHOOL  ;  PHYSICIAN 
TO  THE  GLASGOW  PUBLIC  DISPENSARY  (DEPARTMENT  FOR  KIDNEY  AND 
URINARY  DISEASES)  ;  FORMERLY  SENIOR  ASSISTANT-PHYSICIAN 
TO  THE  GLASGOW  ROYAL  INFIRMARY,  ETC.,  ETC. 


PHILADELPHIA: 
LEA  BROTHERS  & 
1  89  5. 


CO. 


PEEFACE. 


A  large  experience  of  medical  students  has  impressed  me  with 
the  conviction  that  the  importance  which  they  attach  to  the 
examination  of  the  urine,  so  important  in  throwing  light  on 
many  obscure  phenomena  of  disease,  is  usually  not  such'  as  the 
subject  merits.  Nor  are  students  altogether  to  blame  ;  they  are 
rather  to  be  sympathized  with  in  the  enormous  amount  of 
details,  many  of  them  totally  irrelevant  to  the  scientific  practice 
of  medicine  and  surgery,  which  are  embraced  in  the  short 
curriculum  of  study  at  their  disposal,  and  which  consequently 
render  an  accurate  knowledge  of  them  absolutely  impossible. 
Withhrtecent  years  the  department  of  urology  has  so  developed 
as  almost  to  constitute  a  distinct  science.  Many  of  its  minutiae 
are  devoid  of  practical  bearing,  and  many  of  the  constituents 
described  as  existing  in  the  urine,  not  a  few  of  which  I  believe 
to  be  manufactured  in  the  so-called  process  of  isolation,  may  be 
regarded  as  the  curiosities  of  the  chemist's  laboratory.  In  the 
following  pages  I  have  aimed  at  conciseness  and  the  treatment 
of  the  subject  from  the  practical  and  clinical  standpoint. 

I  have  endeavoured  to  incorporate  the  latest  useful  informa- 
tion, and  I  hope  that  the  book  may  prove  acceptable  to  such  as 
are  fully  occupied  in  practice,  and  are  without  ready  access  to 
the  extensive  current  and  other  literature  of  the  subject. 

To  my  friend  and  colleague,  Professor  Eobertson  Watson,  I 
acknowledge  my  cordial  obligations  for  his  invaluable  services 
in  supervising  the  greater  portion  of  the  proofs. 

D.  C.  B. 

Glasgow,  October,  1894. 


CONTENTS. 
PART  I. 


CHAPTER  I. 
ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY. 

Pi 

Semeiology — Size  of  the  Kidney — Weight  of  the  Kidney — Base- 
ment Membrane  or  Stroma  of  the  Kidney — The  Malpighian 
Capsule — The  Glomerulus  —  Circulation  of  Blood  in  the 
Kidney — The  Renal  Vein — Lymphatics  of  the  Kidney — 
Nerves  of  the  Kidney  —  Theories  of  Secretion  of  Urine — 
Relation  between  Urinary  Secretion  and  Arterial  Pressure 
—  Transparency  of  Urine  —  Odour,  Colour,  Fluorescence, 
Temperature,  Quantity  of  Urine — Hydrnria  and  Polyuria — 
Influence  of  Pathological  States — Variation  of  Density  and 
Solid  Residue  in  Disease — Specific  Gravity  of  Urine — Density 
of  Urine — Estimation  of  Total  Solids — Reaction  of  Normal 
Urine — Determination  of  the  Degree  of  Acidity — Alkalinity 
of  the  Urine — Variations  in  Reaction  of  Urine — Chemical 
Composition- of  the  Urine — Toxicity  of  the  Urine — Pathologi- 
cal Sediments  and  Concretions — Accidental  Elements  of  the 
Urine — Reactions  of  Normal  Urine  and  Significance  -  1 


PART  II. 

CHAPTER  II. 

NORMAL  ELEMENTS  OF  THE  URINE. 

History  of  Urea — Description — Physiological  Conditions  which 
modify  the  Amount  of  Urea — Chemistry — Artificial  Pro- 
duction of  Urea,  etc.— Physical  Properties — Combinations  with 


Vlll 


CONTENTS. 


PAGE 

Acids — Extraction  and  Preparation  of  Urea — Quantitative 
Analysis  of  Urea — Process  of  Leconte — Process  of  Millon — 
Process  of  Liebig  —  Volumetric  Analysis  —  Hypobromite 
Process  —  Pathological  Significance  —  Uremia  —  Medicinal 
Agents  which  influence  the  Excretion  of  Urea — Therapeutic 
Indications  -------  42-70 

URIC  ACID. 

Natural  State — Extraction  and  Preparation  of  Uric  Acid — Pro- 
perties of  Uric  Acid — Urates — Acid  Sodium  Urate — Acid 
Potassium  Urate — Acid  Ammonium  Urate — Acid  Calcium 
Urate — Acid  Magnesium  Urate — Lithium  Urate — Tests  for 
Uric  Acid  —  Quantitative  Estimation  of  Uric  Acid  —  Uric 
Acid  in  Albuminous  Urine — Extraction  of  Uric  Acid  from 
Calculi  and  Sediments — Physiological  Relations  of  Uric  Acid 
— Pathology  of  Uric  Acid — Therapeutic  Indications        -  70-83 

HIPPURIC  ACID. 

Extraction — Tests  and  Quantitative   Analysis — Physiology  and 

Pathology   -------  83-86 

CREATINE  AND  CREATININE. 

Extraction  —  Tests  —  Quantitative    Analysis  —  Physiology  and 

Pathology   -------  86-90 

XANTHINE  AND  HYPOXANTHINE. 

Xanthine — Hypoxanthine         -  -  -  -  -  90,  91 

OXALURIC  ACID. 

Oxaluric  Acid    -  -  -  -  -  -  91 

ALLANTOINE. 

Extraction— Tests         -  -  -  -  -  -  91,  92 

SUCCINIC  ACID. 

Extraction— Tests         -  -  -  -  -  -  92,  93 

BENZOIC  ACID. 

Extraction         -  -  -  -  -  -  -  93 

OXALIC  ACID. 

Oxalate  of  Lime — Detection  and  Isolation  from  Urine — Quantita- 
tive Analysis — Physiology  and  Pathology  -  -  -  93-95 


CONTENTS. 


ix 


VOLATILE  ACIDS  (PHENOLS). 

PAGE 

Phenic  Acid — Detection  in  Urine — Hydroquinone — Pyrocatechin 

or  Alkaptone — Indol         -  -  -  -  -  96,  97 

COLOURING  MATTERS. 

Urobiline — Properties  of  Urobiline — Reaction — Pathology — Uro- 
chrome  and  Uroerythrine — Indican — Tests — Uroglaucine — 
Urrhodine   .......  97-101 

PATHOLOGICAL  SIGNIFICANCE  OF  URINE, 

As  from  Colour  and  Density      ....  101,  102 

TO  ESTIMATE  THE  TOTAL  NITROGEN  OF  THE  URINE. 

Kjaldahl's  Method        ......  102 

CHAPTER  III. 

NORMAL  ELEMENTS  OF  THE  URINE  (continued). 

Inorganic  Substances. — Chloride  of  Sodium  —  Qualitative  and 
Quantitative  Analysis— Pathological  Significance — Sulphuric 
Acid  and  Sulphates — Analysis — Quantitative  Analysis  of 
Sulphuric  Acid  and  of  Sulphur — Pathological  Significance  — 
Phosphoric  Acid  and  Phosphates — Phosphoglyceric  Acid — 
Qualitative  and  Quantitative  Analysis  of  Phosphoric  Acid — 
Variations  of  Phosphoric  Acid  in  Urine — Potash,  Soda, 
Lime,  and  Magnesia  —  Qualitative  and  Quantitative 
Analysis — Ammonia,  Iron,  Nitric  Acid,  and  Nitrates  and 
Nitrites — Silica — Peroxide  of  Hydrogen — Gases  in  Urine  103-117 


PART  III. 


CHAPTER  IV. 

ABNORMAL  CONSTITUENTS  OF  THE  URINE. 

Classification  of  Albumens — Properties  of  Albumen — Coagulation 
by  Heat — Coagulation  by  Nitric  Acid — Tests  for  Albumen — 
Fallacies  in  Heat  Test — The  Nitric  Acid  Test — Fallacies  in 


X 


CONTENTS. 


PAGE 

Nitric  Acid  Test — Tanret's  Reagent — Picric  Acid  Test — 
Ferrocyanide  of  Potassium  Test — Nitro-prussiate  of  Soda 
Test — Sodium  Tungstate  Test — Spiegler's  Test — Stutz's  Test 
— Roch's  Test — Jaworowski's  Test — Other  Tests  for  Albumen 
— Mixed  Albuminuria — Relative  Value  and  Delicacy  of  Various 
Albumen  Tests — Quantitative  Analysis — Process  of  Tanret 
and  Troyes — Bodeker's  Method — Process  of  Brandberg — 
Esbach's  Process — Zahor's  Method — Pathological  Significance 
— Therapeutic  Indications — Purulent  Albuminous  Urine  118-147 

Globuline  (Paraglobuline  ;  Fibrinoplastic  Substance) :  Quantita- 
tive Analysis — Process  of  Hammarstein— Pathological  Sig- 
nificance --------  147-150 

Fibrine;  Murine  :  Properties  of  Mucus— Analysis   -  -  150-151 

Leucomaines  and  Ptomaines  -  -  -  -  -  152 

PEPTONES. 

Properties  of  Peptones — Analysis — Process  of  Hofmeister — Re- 
action with  Tanrec's  Solution — Reaction  with  Millon's  Solution 
— Reaction  with  Tannin — Picric  Acid  Reaction — Pathological 
Significance  —  Hemi-albumose  (Propeptone)  —  Properties — 
Analysis  -  -  -  -  -  -  152-154 

Transitory  Albuminuria  :  Pathological  Significance  -  -  155-157 

GLUCOSE  (DIABETIC  SUGAR). 

History — Chemistry  of  Sugar — Tests  for  Sugar  in  the  Urine — 
Trommer's  Reaction — Fallacies  of  Trommer's  Test — Fehling's 
Reaction — Fallacies  of  Fehling's  Test — Purdy's  Method  of 
Estimating  Sugar  in  the  Urine — Schmiedeberg's  Solution — 
Crismer's  Test  —  Bismuth  Reaction  of  Bottger  —  Hoppe- 
Seyler's  Reaction — Almen's  Reaction— Indigo  Reaction — 
Phenyl-Hydrazine  Reaction — Agnosti's  Reaction — Picric  Acid 
Reaction — Fermentation  Test— Specific  Gravity  of  Diabetic 
Urine— Quantitative  Analysis— Urine  containing  less  than 


CONTENTS. 


xi 


PAGE 

5  per  cent.  Sugar—  Duhomme's  Quantitative  Analysis — 
Approximate  Estimate  of  Sugar  by  Specific  Gravity — Gerrard's 
Percentage  Glycosometer — Optical  Quantitative  Analysis — 
Pathological  Significance  —  Idiopathic  Glycosuria  —  Thera- 
peutic Indications — Simulated  Glycosuria         -  -  158-177 

LEVULOSE,  LACTOSE,  INOSITE. 

Levulose — Lactose — Inosite  -----  177-179 

CYSTINE. 

Characters  and  Properties — Analysis-  -  -  -  179-180 

TYROSINE  AND  LEUCINE. 

Properties  —  Pathological   Significance  —  Leucine  —  Properties — 

Pathological  Significance — Analysis       -  -  -  180-182 

ACETONE. 

History  of  Acetone — Properties — Chautard's  Test — Orthonitro- 
benzaldehyde  Reaction — Extraction  of  Acetone  from  Urine — 
Quantitative  Analysis — Pathological  Significance — Various 
Forms  of  Acetonuria       -----  183-187 

MELANINE,  DIVERSE  ACIDS. 

Melanine — Diverse  Acids      -  -  -  -  -  187 

BILE  ELEMENTS. 

Bile  Elements — Mucine  of  Bile — Biliary  Pigments  :  Bilirubine, 
Biliverdine,  Biliprasine,  Bilifuscine,  Bilihumine — Detection  of 
Colouring  Matter  of  Bile  in  Urine — Gmelin's  Reaction — 
Analysis  —  Rosenbach's  Modification  of  Gmelin's  Test — 
Huppert's  Reaction — Bile  Acids :  Choleic  or  Taurocholic 
Acid,  Glycocholic  Acid,  Cholalic  Acid — Reaction  of  Bile 
Acids  (Pettenkofer's  Reaction) -Cholesterine — Analysis  — 
Pathological  Significance  -  -  -  -  188-194 


FATTY  MATTER. 

Lipuria — Chyluria — Galacturia — Detection  of  Fat  in  the  Urine — 

Pathological  Significance  -  195-196 


Xll 


CONTENTS. 


TUBE-CASTS. 

TAGE 

Granular  Cylinders — Granulo -Fatty  Cylinders — Amyloid  Casts  or 
Cylinders— Hyaline  Cylinders— Cylindroids  (Pseudo-Cylin- 
ders)— Spermatic  Cylinders — Epithelial  Cylinders — Hemor- 
rhagic Casts  —  Pathological  Significance  and  Diagnostic 
Value      .......  196-200 

CHAPTER  V. 

ABNORMAL  CONSTITUENTS  OF  THE  URINE  (continued). 

Carbonate  of  Ammonia — Ammonio-Phosphate  of  Magnesia — 
Phosphate  of  Soda  and  Ammonia — Acid  Ammonium  Urate 
— Analysis  of  Ammonia  Salts — Sulphuretted  Hydrogen  201-203 

ORGANIZED  SUBSTANCES. 

Blood  Corpuscles — Hematuria — Hemoglobinuria — Heller's  Re- 
action— Guaiacum  Reaction — Haemin  Reaction — Lechine's 
Reaction — Microscopic  Examination — Pathological  Signifi- 
cance— Renal  Hemorrhage — Spectrum  Analysis — Leucocytes 
(Pus) — Day's  Test  for  Pus — Mucus — Epithelial  Cells — Sper- 
matozoa— Organisms  found  in  Urine      -  -  -  203-214 

CHAPTER  VI. 
SEDIMENTS. 

Examination  of  Sediments — Non-Oganized  Sediments — Distinctive 
Characters — Sediments  in  Acid  Urine — Sediments  in  Alkaline 
Urine — Uric  Acid  and  Urates— Characters  of  Urates — 
Ammonium  Urate — Uric  Acid  Sediments — Hippuric  Acid — 
Oxalate  of  Lime — Triple  Phosphates — Phosphate  of  Lime 
— Carbonate  of  Lime — Sulphate  of  Lime  —  Cystine — Xanthine 
— Tyrosine — Bilirubine — Uroglaucine,  or  Indigotine — Hema- 
toidine — Cholesterine      .....  215-225 

CHAPTER  VII. 


TO  DETERMINE  THE  CHEMICAL  COMPOSITION  OF  A 

CALCULUS  ....  -  226-229 


CONTENTS. 


xiii 


CHAPTER  VIII. 
MEDICAMENTS  AND  ACCIDENTAL  ELEMENTS  IN  THE  URINE. 

PAGE 

Alcohol — Antipyrine — Antifebrtne,  or  Acetanilide — Arsenic  and 
Antimony — Alkaloids — Aristol — Bromides — Carbolic  Acid — 
Chloroform — Chloral— Chlorate  of  Potash — Iron — Iodides — 
Iodoform — Kairine — Lithia — Lead  and  Copper — Mercury — 
Naphthaline  —  Naphthol   and    other    Phenols  —  Bethol  — 
Phenacetine — Salicylates — Salol — Saccharine  —  Strontium  — 
Tannin  —  Turpentine  —  Rhubarb  —  Santonine  —  Thalline  — 
Urethan — Filaments  of  Tissues  ;  Grains  of  Starch        -  230-239 
Appendix     -------    240,  241 

Index  -------  242-246 


THE 

URINE  IN  HEALTH  AND  DISEASE 

AND 

URINARY  ANALYSIS 


PART  I. 

CHAPTER  I. 
ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY. 

Semeiology — Size  of  the  Kidney — Weight  of  the  Kidney — Basement 
Membrane  or  Stroma  of  the  Kidney— The  Malpighian  Capsule — 
The  Glomerulus — Circulation  of  Blood  in  the  Kidney — The  Renal 
Vein — Lymphatics  of  the  Kidney — Nerves  of  the  Kidney — Theories 
of  Secretion  of  Urine — Relation  between  Urinary  Secretion  and 
Arterial  Pressure — Transparency  of  Urine  — Odour,  Colour,  Fluor- 
escence, Temperature,  Quantity  of  Urine — Hydruria  and  Polyuria 
— Influence  of  Pathological  States  —Variation  of  Density  and  Solid 
Residue  in  Disease— Specific  Gravity  of  Urine — Density  of  Urine 
— Estimation  of  Total  Solids — Reaction  of  Normal  Urine — Deter- 
mination of  the  Degree  of  Acidity — Alkalinity  of  Urine — Variation? 
in  Reaction  of  Urine— Chemical  Composition  of  the  Urine —Toxicity 
of  the  Urine— Pathological  Sediments  and  Concretions — Accidental 
Elements  of  the  Urine — Reactions  of  Normal  Urine  and  Signifi- 
cance. 

By  the  department  of  medicine  termed  semeiology  (arjuElov,  a 
sign)  is  understood  that  which  treats  of  the  signs  of  disease  as 
illustrating  and  explaining  the  nature  of  the  departure  from 
health  with  which  these  signs  are  associated,  and  of  which  they 
are  the  evidences.  In  this  there  is  of  necessity  implied  a  know- 
ledge of  the  healthy  functions  and  a  valid  process  of  deductive 

1 


2 


THE  URINE  IN  HEALTH  AND  DISEASE. 


reasoning.  The  functions  of  the  kidney,  and  the  significance 
attached  to  the  modifications  and  varieties  of  its  secretion 
and  excretion  as  bearing  upon  disease  and  indicating  rational 
treatment,  have  engaged  attention  from  the  birth  of  medicine 
as  a  science.  Two  organs,  placed  in  the  abdominal  cavity, 
but  outside  the  peritoneum,  the  kidneys  are  situated  on  either 
side  of  the  vertebral  column  in  the  lumbar  region.  The  right 
kidney  is  usually  placed  at  a  lower  level  than  the  left.  The 
appearance  of  the  kidney  is  so  characteristic  that  the  term 
reniform  is  usually  employed  to  describe  it  and  bodies  of  a 
similar  form.  It  has  not  inaptly  been  compared  in  outline  to 
that  of  a  haricot-bean,  the  hilus,  or  depression,  through  which 
the  ureter,  the  blood-vessels  and  nerves  enter  being  directed 
towards  the  spine. 

As  a  rule,  the  two  kidneys  are  identical  in  size  ;  but  occasionally 
differences  in  size  are  encountered  as  abnormalities  quite  com- 
patible with  health.  In  certain  rare  instances  but  one  kidney 
exists,  this  abnormality  arising  from  an  intra-uterine  coalescence 
of  the  two  primitive  glands. 

The  Size  of  the  Kidney  varies  with  age,  sex  and  general 
development  of  the  individual.  Ordinarily  the  kidneys  measure 
about  4  inches  in  length,  2^  inches  in  breadth,  and  1\  inches 
or  more  in  thickness.  The  left  kidney  is  sometimes  the  longer 
and  thinner,  the  right  being  shorter  and  wider. 

The  Weight  of  the  Kidney  likewise  varies  with  age  and 
development.  In  the  adult  male  it  usually  weighs  about  4J- 
ounces,  being  somewhat  less  in  the  female.  According  to 
Glendinning,  the  two  kidneys  of  the  male  weigh  on  an  average 
ounces,  and  those  of  the  female  9  ounces.  According  to 
the  observations  of  Eeid,  the  average  weights  of  the  kidneys 
are,  in  160  observations  by  him,  4£  to  6  ounces  in  the  adult 
male,  and  in  the  adult  female  (74  observations)  4  to  ounces. 
The  specific  gravity  of  the  renal  substance  is  1052.  The 
superficial  colour  of  the  kidney  is  a  deep  reddish-brown. 

Chemically  the  kidney  contains  83  per  cent,  of  water,  1  per 
cent,  of  fatty  matter,  and  the  16  remaining  constituents  almost 
exclusively  represent  albuminoid  compounds. 

Like  all  other  glands,  the  kidney  may  be  structurally  regarded 
as  composed  of  a  basement  membrane  or  matrix ;  a  series  of  tubes 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  3 

for  depuratory  purposes  communicating  directly  or  indirectly 
with  the  exterior ;  a  system  of  cells  for  separating  and 
elaborating  the  ultimate  products  of  waste ;  a  system  of  blood- 
vessels supplying  nourishment  to  the  organ  and  conveying  to  it 
the  products  to  be  secreted  and  excreted ;  and  a  system  of  nerves 
regulating  the  circulation  of  the  blood.  Independently  of  these, 
the  kidney  possesses  a  lymphatic  system.  The  functions 
performed  by  the  kidney  in  the  aggregate  are  simply  those  per- 
formed by  the  single  cell,  and  may  be  classified  as  physical, 
vital,  and  chemical;  the  physical  consisting  of  dialysis  and 
taking  place  in  the  glomerulus  and  Malpighian  capsule  ;  the  vital 
in  the  special  selection  manifested  by  the  glandular  structure  in 
the  discharge  of  the  function  of  excretion ;  and  the  chemical  in 
the  elaboration  and  the  separation  of  the  ultimate  products  of 
oxidation  in  the  body. 

The  Basement  Membrane  or  Stroma  of  the  Kidney.— 
Externally  the  kidney  is  invested  by  a  thin  and  strong  fibrous 
coat,  the  tunica  propria,  which  is  loosely  attached  to  its 
substance  by  a  delicate  areolar  tissue  and  minute  bloodvessels. 
Prolongations  from  the  tunica  propria  extend  inwards  in  the 
tissue  of  the  organ,  and  are  continuous  with  the  connective 
tissue  proper  presently  to  be  noticed.  When  the  tunica  propria 
is  traced  to  the  liilus,  it  is  found  to  be  continuous  with  the 
external  surface  of  the  infundibulum  formed  by  the  dilated 
portion  of  the  emergent  ureter,  and  the  adherent  nutrient 
bloodvessels  which  enter  at  this  part.  On  making  a  section  of 
the  kidney  from  its  outer  to  its  inner  border  the  fissure,  or  hilus, 
is  found  to  extend  some  distance  into  the  organ,  forming  a  cavity 
termed  the  sinus,  into  the  bottom  of  which  the  fibrous  coat  can 
be  traced.  The  emergent  ureter  is  greatly  enlarged  before  it 
leaves  the  organ  by  the  union  of  its  primary  subdivisions  forming 
a  chamber  termed  the  pelvis.  Into  the  substance  of  the  organ 
prolongations  of  the  ureter  pass  which  terminate  abruptly  in 
cup-like  depressions  called  the  calyces,  into  which  little  conical 
protrusions  depend — the  Malpighian  pyramids.  The  outer 
capsule  of  the  kidney  consists  of  connective  tissue  chiefly  of  the 
white  fibrous  variety,  which,  on  being  examined  with  a  high 
power,  is  found  to  contain  flattened  connective  tissue  corpuscles. 
This  tissue  is  most  compactly  arranged  towards  the  periphery, 


4 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


becoming  areolar  in  its  deeper  portion,  the  tenuity  of  its 
fibres  increasing  as  it  dips  down  and  becomes  continuous  with 
the  intertubular  tissue  of  the  subjacent  cortex.  Between  the 
cortex  and  the  capsule  there  is  a  system  of  bloodvessels  and 
elongated  cells,  described  by  Eberth  as  a  plexus  of  non-striated 
muscular  fibres. 

The  existence  of  connective  tissue  in  the  kidney,  long  dis- 
puted, was  first  maintained  by  Goodsir.  This  view  was  after- 
wards combated  by  Von  Wittich,  who  maintained  that  the 
interstices  of  the  secretory  and  excretory  portions  of  the  kidney 
were  merely  separated  by  capillary  vessels.  This  opinion  held 
ground,  especially  among  German  histologists,  until  Arnold  Beer 
published  the  results  of  his  investigations.*  The  connective  tissue 
in  the  normal  state  is  found  in  greatest  abundance  at  the  level 
of  the  hilus,  and  is  distributed  along  the  bloodvessels,  and  serves 
to  support  them  in  the  same  manner  as  that  of  the  liver.  As  the 
connective  tissue  is  traced  inwards  from  the  papillae  it  becomes 
less  manifest.  It  contains  cell  elements,  fibres,  and,  according  to 
Ludwig,  lacunar  spaces  in  connection  with  the  lymphatic  system. 
Processes  of  the  connective  tissue,  as  we  have  seen,  dip  inwards 
from  the  capsule  into  the  cortical  substance,  and,  like  the  con- 
nective tissue  in  other  glands,  these  enlarge  on  the  supervention 
of  interstitial  change,  and  undergo  contraction  and  other  morbid 
changes,  thus  destroying  the  glandular  tissue  and  abrogating  its 
proper  function,  the  whole  process  being  the  sequence  of  initial 
hyperaemia  abnormally  protracted.  This  multiplication  and 
change  of  connective  tissue  is  an  important  factor  in  a  large 
class  of  diseases,  not  only  in  the  kidney,  but  in  the  lungs,  liver, 
and  spinal-cord,  etc.  (cirrhosis).  It  is  in  it  that  abscesses  form, 
and  that  the  great  bulk  of  neoplasms  are  developed.  Axel  Key 
first  noticed  that  connective  tissue  exists  .in  the  glomerulus, 
binding  together  the  capillary  loops,  and  becoming  continuous 
with  the  tissue  which  surrounds  the  afferent  arterioles,  and  the 
medullary  substance  of  which  they  are  branches.  From  there 
the  tissue  may  be  traced  round  the  arteriolar  rectae  into  the 
boundary  layer  between  the  medulla  and  the  cortex,  when  it 

*  'On  the  Connective  Tissue  of  the  Human  Kidney  in  its  Physio- 
logical and  Pathological  Relations, '  1859. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  5 

becomes  scanty  and  assumes  a  hyaline,  honeycombed,  mem- 
branous aspect.  According  to  Schweigger-Seidel,  in  this  situa- 
tion the  connective  tissue  may  be  branched  or  spindle-shaped 
and  possess  oval  nuclei  disposed  transversely  to  the  long  axis  of 
the  tubules.  On  macroscopic  (ftaicpug,  great)  examination  a 
section  of  the  kidney  shows  certain  clearly-defined  differentiation 
of  structure.  Fundamentally,  the  gland  is  seen  to  be  com- 
posed of  an  external  or  cortical  portion,  and  a  medullary 
portion  directed  from  the  cortex  towards  the  hilus.  The  cor- 
tical portion  occupies  the  entire  surface  of  the  organ,  is  of  a 
dark-brown  chestnut  colour,  and  forms  a  layer  of  about  two 
lines  in  thickness.  It  is  friable,  easily  lacerated,  and  when 
this  does  take  place  the  laceration  usually  happens  in  a  direc- 
tion vertical  to  the  surface.  The  rupture  presents  an  irregular 
appearance  due  to  an  admixture  of  straight  and  convoluted  tubes 
and  Malpighian  bodies. 

From  the  cortical  substance,  and  passing  towards  the  hilus, 
prolongations  are  sent,  which  separate  and  form  partitions 
between  the  pyramids  of  Malpighi.  These  septa  terminate  near 
the  summit  of  the  papilla,  and  are  known  as  the  columns  of 
Bertini  (septula  renum).  It  is  in  the  cortical  substance  and  its 
prolongations  that  morbid  changes  are  most  frequently  found. 

Between  the  septula  renum  another  collection  of  tubes  is 
seen,  constituting  the  pyramids  of  Malpighi,  the  bases  of  which 
are  directed  towards  the  cortex  of  the  organ,  and  their  apices 
towards  the  hilus,  terminating  in  the  papillae  which  open  into  the 
calyces.  The  number  of  these  pyramids  varies  from  eight  to 
eighteen.  In  ultimate  structure  these  pyramids  are  composed  of 
a  series  of  straight  tubes  (tubes  of  Bellini)  placed  parallel  to  the 
axis  of  the  pyramid,  and  presenting  a  striated  aspect.  Passing 
towards  the  cortex,  these  tubes  divide  and  subdivide  at  very 
acute  angles.  At  the  base  of  the  pyramids  of  Malpighi  they 
unite  with  the  convoluted  tubes  ;  and  it  is  this  union  of  the 
collector  with  a  convoluted  tube  which  constitutes  a  pyramid  of 
Ferrein. 

The  Malpighian  Capsule. — By  the  Malpighian  capsule,  or 
capsule  of  Bowman,  is  understood  the  dilated  cortical  extremity 
of  the  uriniferous  tubule,  whose  other  extremity  terminates  in 


18 

18 

Fig.  1. — General  View  of  the  Structure  of  the  Kidney  (the 
tubes  of  Henle  not  represented). 

1,  Renal  vein  ;  2,  Renal  artery  ;  3,  Ureter,  continuous  with  the  open 
pelvis  ;  4,  Cut  cortex  of  the  kidney  ;  5,  Surface  of  the  kidney  ;  6,  Cor- 
tical substance  ;  7,  A  Malpighian  pyramid  with  its  arteries  :  8  8,  Papillae 
of  pyramids  which  have  not  been  divided  ;  9,  A  divided  calyx, 
embracing  a  pyramid  ;  10,  Branch  of  the  renal  artery  between  two 
pyramids  ;  11,  Malpighian  capsule  magnified  40  diameters  ;  12,  Vessels 
in  the  centre  of  the  glomerulus  ;  13  Efferent  vessel  of  the  glomerulus  ; 
14,  Capillary  network  ;  15,  Convoluted  tube  of  the  cortical  substance 
x  20  ;  16,  Tortuosities  of  convoluted  tube  ;  17,  Tortuous  tubes  x  40  ; 
18  18  18,  Glomeruli  x  10  x  20  ;  19,  Tortuous  tubes  x  20  to  25  ;  20, 
Some  tube3  cut. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY. 


7 


the  papilla.  It  embraces  within  its  walls  a  tuft  or  network  of 
bloodvessels,  termed  the  glomerulus,  from  which  vessels  the 
urine,  with  certain  of  its  diffusible  salts,  is  secreted.  In  structure 
the  capsule  consists  of  a  hyaline  membr ana  propria,  thickened, 
according  to  Ludwig,  externally  by  a  greater  or  less  proportion 
of  a  delicate  fibrous  tissue  dipping  inwards  to  form  an  invest- 
ment for  the  glomerulus.  The  inner  surface  of  the  capsule  is 
lined  by  a  layer  of  epithelial  cells.  These  cells  undergo  certain 
physical  changes,  according  to  age.  In  early  life  they  are  some- 
what polyhedral  in  form,  while  as  age  advances  they  become 
flattened.  They  all  possess  well-marked  oval  nuclei,  which 
may  be  distinctly  revealed  by  injecting  the  renal  bloodvessels 
with  a  solution  of  nitrate  of  silver.  In  like  manner  the  glome- 
rulus is  covered  with  its  own  special  epithelial  cells,  which  are 
considerably  larger  than  those  lining  the  capsule,  and  remain  of 


Fig.  2. — Diagram  showing  the  Relation  of  the  Malpighian 
Body  to  the  Uriniferous  Ducts  and  Bloodvessels.  (After 
Bowman.) 

a,  One  of  the  interlobular  arteries  ;  d,  Afferent  artery  passing  into  the 
glomerulus  ;  m,  Vascular  tuft  formed  within  the  glomerulus  ;  c,  Capsule 
of  the  Malpighian  body  (capsule  of  Bowman)  forming  the  termination 
of  and  continuous  with  t,  the  uriniferous  tube  ;  e  6,  Efferent  vessels 
which  subdivide  into  the  plexus  p,  surrounding  the  tube,  and  finally 
terminate  in  a  branch  of  the  renal  vein  p. 

a  polygonal  shape  (cubical).  These  two  epithelial  layers  con- 
stitute thus  a  closed  sac,  containing  an  excreting  gland. 

The  Glomerulus. — The  glomerulus  is  a  tuft  of  bloodvessels 
composed  of  terminal  branches  of  the  renal  artery  and  the 


Fig.  3.— Diagram- 
matic View  of  the 
Loops  of  Henle, 
showing  their  Con- 
nection with  the 
Malpighian  Capsule. 
{After  Gross,  of  Stras- 
burg. ) 

1,   Surface    of  the 


papilla  ;  2,  Surface  of  the 
kidney ;  3,  Commencement 
of  the  medullary  portion 
(between  2  and  3  indicates 
the  extent  of  cortical  sub- 
stance) ;  a  a,  Glomeruli  of 
Malpighi  ;  b  6,  Tubuli  con- 
torti  ;  c  c,  Loops  of  Henle  ; 
g  gy  Canaliculi,  uniting  to 
form  the  canal  of  Bellini — 
the  latter  unite  with  others 
to  form  a  common  canal 
opening  on  the  summit  of 
the  papilla. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY. 


9 


commencing  branches  of  the  venous  system.  On  reaching  the 
Malpighian  capsule,  the  afferent  artery  pierces  its  homogeneous 
envelope  and  breaks  up  into  smaller  tortuous  branches,  which 
ultimately  unite  to  form  an  efferent  vein,  which  makes  its  exit 
from  the  capsule  near  the  entrance  of  the  artery,  and  unites  with 
the  intertubular  venous  plexus  surmounting  the  convoluted 
tubes,  all  of  which  ultimately  join  the  renal  vein. 

At  a  point  opposite  to  the  entrance  of  the  afferent  artery  and 
the  exit  of  the  efferent  vein,  the  glomerulus  becomes  continuous 
with  the  canal  of  the  convoluted  tube.  At  the  point  of  junction 
the  canal  is  narrowed,  and  to  this  portion  the  term  '  neck  of  the 
capsule  '  has  been  applied.  Commencing  at  this  neck,  the  canal, 
situated  in  the  cortical  substance,  becomes  tortuous,  of  consider- 
able size,  and  is  now  designated  the  convoluted  tube,  in  virtue 
of  its  appearance.  After  a  short  course  as  a  convoluted  tube, 
termed  the  proximal  convoluted  iubule,  the  canal  becomes 
narrowed,  and  descends  in  the  form  of  a  straight  tube  towards 
the  papilla.  This  portion  is  termed  the  descending  branch,  or 
the  small  branch  of  the  loop  of  Henle.  Within  a  variable 
distance  of  the  papilla  the  canal  abruptly  bends  upon  itself, 
forming  an  ascending  branch,  or  great  branch  of  the  loop  of 
Henle,  which  runs  parallel  with  the  smaller  one,  and  aga'n 
narrows  into  a  spiral  portion,  then  dilates  into  a  tortuous  tube, 
forming  the  distal  convoluted  tubule,  which  opens  into  a  collect- 
ing or  straight  tubule.  It  is  the  junction  of  the  distal  convo- 
luted tubule  with  the  straight  tubule  which  constitutes  the 
pyramid  of  Ferrein.  The  distal  convoluted  tubule  is  also 
known  as  the  intercalated  portion  (S  dials  tuck,  Schweigger- 
Seidel). 

As  function  is  specialized  in  certain  portions  of  the  kilney,  we 
accordingly  find  that  the  cells  lining  the  secreting  tubes  differ 
correspondingly.  (1)  In  che  proximal  convoluted  tubule  there 
is  a  single  layer  of  epithelial  cells,  which  reduces  its  lumen  to 
about  a  third  of  its  whole  diameter.  In  general  outline  the  cells 
of  this  section  are  somewhat  cubical ;  towards  the  neck  they 
decrease  very  markedly  in  height,  and  have  thus  the  appearance 
of  ceasing  abruptly  there.  They  vary  in  size  throughout  the 
tubule,  and  their  opposed  sides  are  not  straight,  but  slightly 


10 


THE  URINE  IN  HEALTH  AND  DISEASE. 


Fig.  4.— Diagram 
of  the  Looped 
Uriniferous  Tubes, 
and  their  connec- 
TION with  the  Cap- 
sules of  the  Glo- 
me r  u  l  i.  ( From 
Southey,  after  Lud- 
wig.) 

In  the  lower  part 
of  the  figure  one  of 
the  larger  branching 
tubes  is  shown  open- 
ing on  a  papilla  ;  in 
the  middle  part  three 
of  the  looped  small 


tubes  are  seen  de- 
scending to  form  their 
loops  (their  relative 
size  is  not  so  well  indi- 
cated here  as  in  Gross's 
figure  on  page  8.  The 
ascending  branch  is 
about  thrice  the  size  of 
the  descending).  In  the 
upper,  or  cortical  part, 
two  of  these  tubes,  after 
some  enlargement,  are 
represented  as  becom- 
ing convoluted,  and 
dilated  in  the  capsules 
of  the  glomeruli. 


curved,  the  convexity  of  the  one  side  fitting  into  the  concavity  of 
that  in  juxtaposition  with  it.  All  the  cells  possess  central  spherical 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  11 

nuclei.  Klein  describes  the  structure  of  these  cells  as  consist- 
ing of  a  honeycombed  network.  (2)  In  the  spiral  tubule  of 
Schachowa,  the  relative  size,  shape  of  the  walls,  and  lumen 
resemble  the  proximal  convoluted  tubule.  The  cells  at  the 
commencement  of  this  section  are  very  irregular  in  shape,  some 
of  them  being  elongated  columnar  cells  with  concave  sides, 
while  others  are  broad  with  convex  sides  and  convex  free 
surfaces,  thus  resembling  mushrooms,  and  called  the  fungoid 
cells  of  Schachowa.  They  all  possess  centrally-situated  spherical 
nuclei.  (3)  In  the  descending  limb  of  Henle's  loop  the 
epithelial  cells  become  attenuated,  and  contain  oval,  flattened, 
centrally-placed  nuclei.  (4)  In  the  ascending  limb  of  the  loop 
of  Henle  the  epithelial  cells  become  modified  into  polyhedral 
forms  with  a  based  rod-like  striation.  Each  cell  possesses  a 
strongly-marked  spherical  nucleus,  situated  towards  the  free 
extremity,  which  projects  into  the  lumen.  (5)  In  the  spiral 
portion  of  the  ascending  limb  of  Henle's  loop  the  epithelial  cells 
contain  oval,  irregular,  and  flattened  nuclei  placed  towards  the 
lumen,  which  is  almost  obliterated  by  the  large  size  of  the  poly- 
hedral striated  cells.  (6)  In  the  cortical  portion  of  the  ascend- 
ing limb  of  Henle's  loop  the  cells  show  rod-like  structure  at 
their  attached  bases,  and  possess  flattened  or  angular  peripheral 
nuclei,  occasionally  with  imbricated  processes.  (7)  In  the 
irregular  tubule  the  epithelial  cells  are  imbricated,  and  exhibit 
the  rod-like  structure  more  markedly  than  in  any  other  portion 
of  the  renal  tube.  Each  cell  contains  an  oval  or  angular 
nucleus  towards  its  periphery.  (8)  The  intercalated  section  is 
identical  in  location  and  structure  with  the  proximal  convoluted 
tubule.  (9)  The  straight  section  of  the  collecting-tube  has  a 
small  but  distinct  lumen  with  a  single  layer  of  homogeneous 
cells,  varying  in  shape  from  regular  polyhedral  to  flattened  or 
spindle-shaped  elements.  The  cells  possess  ovoid  or  spherical 
nuclei,  and  may  show  imbricated  processes.  (10)  The  collecting- 
tube  of  the  boundary  layer  is  lined  with  epithelial  cells  of  a 
short  columnar  variety,  resembling  those  of  the  foregoing- 
portions.  (11)  In  the  collecting-tubes  and  ducts  of  the  papillary 
portion  the  size  of  the  lumen  and  its  epithelial  cells  depends  on 
the  diameter  of  the  tube,  which  increases  by  the  successive 


Fig.  5.— Dia- 
ghammatic  Re- 
presentation of 
a  Part  of  the 
Straight  and 
Convoluted 
Uriniferous 
Tubes  with  the 
Glomeruli. 
{From  Frey, 
after  a  drawing 
by  Midler.) 

b  b,  Two  large 
straight  tubes  in 
the  medullary 
substance  of  the 
pyramid  ;  c,  Con- 


voluted tubes,  several 
of  their  terminations 
in  the  Malpighian 
capsules,  as  in  d  ;  a, 
Three  arteries  pass- 
ing up  the  pyramid, 
and  dividing  into 
branches  to  the  glo- 
meruli ;  the  efferent 
ves  els  are  also  repre- 
sented, and  the  net- 
work of  capillaries 
between  them  and  the 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  13 

union  of  smaller  ducts,  until  it  forms  ths  large  duct  of  Bellini, 
which  debouches  on  the  papilla. 

Circulation  of  Blood  in  the  Kidney. — The  kidneys  are 
abundantly  supplied  with  blood  through  the  renal  arteries,  which 
branch  off  from  the  aorta  between  the  two  mesenteric  arteries. 
Each  is  directed  outwards  so  as  to  form  nearly  a  right  angle 
with  the  aorta.  Owing  to  the  position  of  the  aorta  on  the 
spine,  the  right  renal  artery,  in  order  to  reach  the  kidney,  has 
a  longer  course  than  the  left,  and  it  runs  behind  the  vena  cava. 
Both  arteries  are  covered  by  the  renal  veins.  Kelatively  to  the 
size  of  the  kidney  the  renal  artery  is  large,  and  the  organ  is  thus 
highly  vascular.  On  reaching  the  hilus  the  renal  artery  enters 
the  organ  between  the  renal  vein  and  the  ureter,  and  usually 
divides  into  four  or  five  primary  branches,  which  may  be  seen 
in  the  sinus  to  pass  in  amongst  the  infundibula.  These  branches 
are  usually  surrounded  by  a  large  proportion  of  adipose  tissue. 
The  arteries  now  further  divide  and  subdivide  to  enter  between 
the  Malpighian  pyramids,  that  is  to  say,  in  the  substance  of  the 
columns  of  Bertini.  They  are  surrounded  by  longitudinal  and 
circular  bands  of  muscular  fibres,  and  by  a  delicate  connective 
tissue,  which  accompanies  them  in  their  course  throughout  the 
papillary  region.  A  little  before  reaching  the  base  of  the  pyramid 
they  divide  and  anastomose  between  one  another,  the  inter- 
communicating arterial  network  fo  ming  an  arterial  incomplete 
arch,  whose  convexity  is  towards  the  surface  of  the  kidney.  By 
its  concavity  this  arch  gives  branches  to  the  pyramids,  and  by 
its  convexity  it  furnishes  numerous  branches  proceeding  per- 
pendicularly towards  the  cortical  substance.  In  the  course  of 
these  branches  short,  transverse  off-shoots  are  distributed  (in 
the  cortical  substance),  one  to  each  Malpighian  capsule  forming 
its  afferent  artery,  and  breaking  up  in  the  loop,  forms  terminal 
branches  anastomosing  with  the  efferent  vein.  Occasionally  the 
afferent  arterioles  give  off  lateral  branches  before  they  reach  the 
glomerulus,  which  ramify  around  the  convoluted  tubules.  In 
the  portion  of  the  cortical  substance  which  is  devoid  of  Mal- 
pighian capsules,  the  interlobular  arteries  either  terminate  as 
afferent  arteriolar,  or  continue  towards  the  capsule,  supplying  the 
network  of  capillaries  surrounding  the  convoluted  tubes,  or 


14 


THE  URINE  IN  HEALTH  AND  DISEASE. 


anastomose  with  branches  from  the  lumbar  artery,  with  which 
the  capsule  is  thus  supplied.  It  is  thus  obvious  that  the  kidney 
has  a  blood- supply  independently  of  the  renal  artery  ;  and  thus, 
if  the  renal  artery  be  tied,  the  kidney  may  be  injected  through 
the  aorta  by  means  of  these  lumbar  branches.    From  the  larger 


Fig.  6.  Semidiagrammatic  Re- 
presentation OF  A  MALP1GHIAN 
Body  in  its  Relation  to  the 
Uriniferous  Tube.  {From  Kbl- 
liker. ) 

or,  Capsule  of  the  Malpighian 
body  continuous  with  b,  the  mem- 
brana  propria  of  the  coiled  ur  ini- 
ferous tube ;  c.  Epithelium  of  the 
Malpighian  body ;  d,  Epithelium 
of  the  uriniferous  tube  ;  e,  De- 
tached epithelium  ;  ft  Afferent 
vessel  ;  g,  Efferent  vessel ;  h,  Con- 
voluted vessels  of  the  glomerulus. 


Fig.  7. — Three  Malpighian 
Capsules  in  Connection  with 
the  Bloodvessels  and  the 
Urinary  Tubes  of  the  Human 
Kidney.  {From  Koiliker,  after 
Bowman  ) 

a,  Termination  of  an  intertubu- 
lar  artery  ;  b,  Afferent  arteries  ; 
e,  A  denuded  vascular  glomerulus  ; 
(Z,  Efferent  vessel  ;  e,  Two  of  the 
glomeruli  enclosed  by  the  Mal- 
pighian capsules  ;  f,  Uriniferous 
tubes  connected  with  them. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  15 

arterial  branches  existing  between  the  cortex  and  the  medullary 
structure  another  system  of  branches  arises.  Those  entering  the 
boundary  layer  proceed  towards  the  papilla  in  groups  parallel 
with  and  between  the  renal  tubules.  These  are  the  arteriohv 
rectcB,  which  impart  the  peculiar  banded  appearance  to  the 
medullary  rays.  As  they  approach  the  papilla  they  decrease  in 
number  owing  to  the  lateral  branches  which  they  give  off,  and 
around  the  mouths  of  the  ducts  they  terminate  in  a  network 
of  capillaries  continuous  with  the  vence  rectce,  which  pursue  an 
opposite  direction  directly  parallel. 

The  Renal  Vein  originates  in  the  efferent  vessel  of  the 
glomerulus  and  the  capillary  venous  system  of  the  kidney 
generally.  The  efferent  vessel,  as  we  have  seen,  considerably 
smaller  than  the  afferent,  originates  in  the  Malpighian  tuft. 
Penetrating  in  its  outward  passage  the  Malpighian  capsule  near 
the  entrance  of  the  afferent  vessel,  it  breaks  up  into  a  dense 
network  of  veins,  which  surround  the  convoluted  tubes  and 
closely  embrace  them.  The  meshes  of  the  labyrinth  and  peri- 
phery are  smaller  and  more  regular  in  disposition  than  those  in 
the  medullary  structure,  which  become  more  elongated.  The 
capillaries  of  the  periphery  of  the  cortex  open  into  minute 
veinlets,  which  again  empty  into  larger  vessels  forming  rays,  and 
hence  termed  vence  stellatce.  The  vence  stellatce  become  inter- 
lobular veins,  and  accompanying  the  interlobular  artery  between 
the  cortex  and  the  medulla,  form  a  venous  arch,  hi  which 
the  vence  rectce,  commencing  in  the  papilla,  terminate. 

The  blood  in  the  efferent  vein  of  the  glomerulus  is  still  red, 
and  hence  this  vessel  is  sometimes  termed  an  artery.  The 
specific  urinary  constituents,  such  as  urea,  hippuric  acid,  etc., 
are  not  separated  from  it  until  it  reaches  the  convoluted  tubes. 
Unlike  all  the  other  venous  blood  of  the  body,  it  is  not  sur- 
charged with  carbonic  acid  gas.  That  of  the  body  in  general  con- 
tains 6  per  cent,  of  oxygen,  while  that  of  the  renal  vein  contains 
16  per  cent.,  or  only  1  per  cent,  less  than  that  of  arterial  blood. 

Lymphatics  of  the  Kidney.— According  to  Sappey,  the 
kidney  possesses  no  superficial  lymphatics,  while  the  origin  of 
the  deep  lymphatics  is  as  yet  undetermined.  They  are  in  free 
communication  with  the  lymph  spaces  which  surround  the  con- 


16  THE  URINE  IN  HEALTH  AND  DISEASE. 

■ 

voluted  tubes  of  the  cortex.  A  plexus  of  lymphatic  vessels  exists 
around  the  larger  bloodvessels  which  enter  the  medulla ;  and, 
according  to  Ludwig  and  Zawarzkin,  a  system  of  intertubular 
lymph  spaces  communicates  freely  with  a  superficial  capsular 
system. 

Nerves  of  the  Kidney. — The  nerves  of  the  kidney  are  derived 
from  the  renal  plexus  and  the  lesser  splanchnic.  They  pass 
into  the  renal  structure  with  the  bloodvessels  ;  and,  according 
to  Pfliiger,  they  terminate  in  the  nuclei  of  the  cells.  The  nervous 
system,  in  all  parts  of  the  body,  controls  and  regulates  the  circu- 
lation of  the  blood,  and  thus  impressions  upon  the  fibres  of  the 
renal  plexus  which  surround  the  tubuli  contorti  must  influence 
the  secretion  of  urine,  and  especially  the  excretion  of  urinary  ) 
products.  Moreau,  in  1868,  pointed  out  that  section  of  the 
splanchnic  nerve  was  followed,  as  in  cholera,  by  an  intestinal 
flux  ;  and  Eckhardt,  in  experiments  which  he  also  performed  on 
the  splanchnics,  found  that  their  section  induced  hyperemia  of 
the  tubuli  contorti,  albuminuria  and  increased  secretion  of  urine. 
Vascular  tension,  or  blood  pressure,  is  one  of  the  physiological 
factors  in  the  secretion  of  urine,  and  thus  we  have  it  artificially 
augmented  to  an  abnormal  degree.  Hyperemia  of  the  kidney 
occurs  likewise  in  cases  of  spinal  paralysis,  and  particularly  when 
the  ganglionic  nerves  are  affected.  Yulpian  found,  as  the  result 
of  observations  on  a  dog  subjected  to  the  influence  of  woorara, 
that  division  of  the  left  splanchnic  was  followed  by  congestion  of 
the  corresponding  kidney,  the  organ  assuming  a  deeper  hue, 
becoming  enlarged,  and  polyuria  and  albuminuria  supervening. 
The  influence  of  the  vaso-constrictor  nerves  is  thereby  suspended. 
The  contrary  condition,  anuria,  is  brought  about  by  an  opposite 
physiological  state,  contraction  of  the  arterioles.  In  Vulpian's 
experiment  there  was  no  extravasation  of  globules  of  blood  nor 
desquamation  of  the  tubes.  What  was  especially  interesting, 
the  renal  vein  became  larger  and  redder.  On  the  peripheric  end 
of  the  cut  nerve  being  subjected  to  the  action  of  electricity,  the 
kidney  and  its  capsule  became  pale.  They  progressively  resumed 
their  reddish  hue  as  the  current  was  suspended,  while  the  size  of 
the  renal  vein  diminished.  Mental  impression  may  act  on  the 
splanchnics  in  a  similar  manner,  and  hence  we  may  witness 


ANATOMY  AND  PHYSIOLOGY  OF  THE   KIDNEY.  17 

polyuria,  and  even  hematuria.  According  to  Byrani  section  of 
the  cervical  sympathetic  diminishes  the  quantity  of  urine,  while 
its  electric  excitation,  on  the  contrary,  augments  it.  Section  of 
the  pneumogastric  seems  to  have  no  influence  over  the  urinary 
secretion.  Bernard  states,  however,  that  he  has  noticed  in  some 
experiments  an  augmentation  of  urine  and  a  congestion  of  the 
kidney  from  excitation  of  the  pneumogastric  below  the  diaphragm. 
Arthaud  and  Butteau,  on  the  contrary,  observed  an  arrest  of 
urinary  secretion  from  excitation  of  the  peripheric  end  of  the 
pneumogastric.  Section  of  the  spinal  marrow  in  the  cervical 
region,  by  causing  a  lowering  of  blood-pressure,  arrests  urinary 
secretion.  Excitation  of  the  lower  portion  of  the  spinal  cord 
produces  the  same  result  by  contraction  of  the  renal  arterioles 
through  the  vaso-motor  nerves.  It  is  interesting  to  note,  how- 
ever, that  if  the  splanchnics  are  previously  divided,  so  as  to 
eliminate  vaso-motor  action,  excitation  of  the  cord  determines 
an  augmentation  of  the  secretion  and  an  increase  of  arterial 
pressure.  Pricking  of  the  fourth  ventricle  causes  polyuria  and 
albuminuria,  or  glycosuria  if  the  lesion  be  too  high  or  too  low. 
The  physiological  factors  in  the  secretion  of  urine  may  be 
regarded  as — (1)  the  function  of  the  glomerulus— osmosis  and 
dialysis  ;  (2)  the  circulation  of  blood  hi  the  kidney — accelerated 
or  slowed  ;  and  (3)  vascular  tension. 

Generally  speaking,  the  blood  in  the  capillaries  of  the 
glomerulus  is  subjected  to  a  greater  pressure,  and  that  of  the 
interstitial  or  parenchymatous  capillaries  of  the  kidney  to  a 
lesser  amount  of  pressure  than  the  blood  of  ordinary  capillaries. 
The  intensity  of  the  pressure  is  such  that,  as  admitted  by  all 
physiologists,  a  purely  mechanical  filtration  might  take  place, 
which  would  at  least  account  for  the  first  part  of  the  urinary 
secretion ;  but  on  the  nature  of  the  fluid  secreted  there  is  a 
disagreement  among  authorities.  Many  theories  have  from  time 
to  time  been  enunciated  as  to  the  urinary  secretion.  The  three 
which  at  present  find  most  acceptance  are  those  of  Bowman, 
Ludwig  and  Kuss. 

The  Theory  of  Bowman.  —  According  to  Bowman,  the 
glomerulus  of  Malpighi  permits  only  the  watery  portion  of  the 
.urine  to  filter  through,  the  solid  parts  of  the  urine  formed  in  the 

2 


13 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


kidney  or  taken  from  the  blood  being  secreted  by  the  cubical 
cells  lining  the  convoluted  tubes,  and- absorbed  by,  or  incorporated 
with,  the  water  as  it  passes  along  the  tubes.  Kecognising  the 
difficulty  of  comprehending  how  the  very  diffusible  salts  of  the 
blood  found  in  the  urine  did  not  pass  through  the  tuft -walls  and 
capsule  with  the  water,  Bowman  himself  and  Yon  Wittich  and 
Donders  so  modified  the  theory  as  to  include  the  nitration  of  the 
diffusible  salines  with  the  water,  while  the  epithelial  cells  of  the 
convoluted  tubes  only  secreted  the  urea  and  the  uric  acid. 
Eecently  Heidenhain  has  reverted  to  the  opinion  of  Bowman, 
endeavouring  to  establish  the  independent  elimination  of  the 
watery  and  the  solid  portions  of  the  urine.  These  two  processes 
seem  really  to  take  place  in  two  different  portions  of  the  kidney. 
According  to  Heidenhain,  the  secretion  of  water  by  the  kidney 
may  be  completely  arrested  without  interfering  with  the  elimina- 
tion of  solid  substances  injected  into  the  blood,  such  as  indigo- 
tate  and  urate  of  soda.  This  elimination  takes  place  through  the 
epithelium  of  the  convoluted  tubes  and  the  larger  branch  of  the 
loop  of  Henle.  If  the  cortical  substance  of  the  kidney  be 
cauterized,  the  secretion  of  urine  is  suspended  in  the  portion  thus 
operated  upon  ;  and  even  in  the  corresponding  region  of  the 
medullary  substance,  whose  canals  in  this  case  do  not  contain 
indigotate  of  soda.  Under  these  circumstances,  however,  Heid- 
enhain has  found  the  cortical  canals  to  be  filled  with  this  colour- 
ing matter  ;  but  the  secretion  of  water  having  been  arrested,  the 
colouring  matter  was  not  drawn  into  the  medullary  canals. 
Hence,  it  is  evident  that  the  aqueous  part  of  the  urinary  secre- 
tion transudes  through  the  glomerulus,  and  presumably  also 
from  the  convoluted  tubes.  Further,  other  considerations  seem 
to  point  to  the  secretion  of  the  watery  portion  of  the  urine  by  all 
portions  of  the  kidney,  the  cortical  as  well  as  the  medullary 
substance.  In  amphibious  animals  the  glomeruli  and  the  renal 
canaliculi  have  an  absolutely  distinct  circulation,  the  glomerulus 
receiving  its  blood  from  the  aorta,  and  the  canaliculi  from  a 
portal  system  analogous  to  that  of  the  liver,  composed  of  venous 
branches  proceeding  from  the  inferior  extremity,  the  oviduct  and 
the  dorso-lumbar  vein.    These  are  the  afferent  renal  veins.  If 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  19 

the  common  aorta  be  tied,  the  glomeruli  receive  no  blood,  and 
consequently  their  function  is  brought  to  a  standstill. 

Theory  of  Ludwig. — According  to  this  theory,  blood-pressure 
performs  the  principal  role  in  the  secretion  of  the  urine.  Under 
the  influence  of  this  pressure,  the  serum  of  the  blood  transudes 
through  the  walls  of  the  capillaries  of  the  glomerulus  minus  the 
albuminates  and  the  fats.  The  fluid  which  escapes  contains 
water,  salts  of  the  blood,  and  extractive  matters.  Having 
reached  the  canaliculi,  this  liquid  finds  itself  in  contact  with  the 
epithelium  of  the  convoluted  tubes,  and  with  the  lymph  which 
surrounds  the  canals,  and  which  is  a  more  concentrated  fluid. 
The  lymphatics  and  the  capillaries  which  surround  the  canaliculi 
take  up  a  portion  of  the  water  and  salts  filtered,  until  the  endos- 
motic  equilibrium  is  established.  Ludwig  primarily  ascribes  no 
role  to  glandular  activity,  and  the  experiments  of  Goll  tend  to 
show  that  blood-pressure  alone  is  the  chief  factor  in  the  process 
of  urinary  transudation.  The  quantity  of  urine  augments  with 
pressure,  and  its  concentration  is  in  an  inverse  ratio  to  the 
rapidity  of  the  secretion,  and  never  exceeds  a  certain  figure.  All 
this  notwithstanding,  the  proportion  of  the  urinary  principles 
and  of  the  blood  cannot  be  explained  on  purely  physical  laws. 
And  hence,  even  admitting  the  theory  of  Ludwig,  the  element  of 
glandular  activity  requires  to  be  invoked.  An  outstanding  diffi- 
culty of  this  theory  is  the  question  why  the  albumen  of  the  blood 
does  not  pass  through  the  glomerulus  with  the  other  constituents. 
Ludwig' s  explanation  of  this  is  that  the  albumen  diffuses  with 
great  difficulty  in  presence  of  the  free  acid  of  the  urine  which  is 
formed  in  the  kidney ;  but  it  is  not  in  the  glomerulus  that  this 
acid  is  formed,  and  it  is  here  that  the  filtration  takes  place. 
Normally  the  albumen  does  not  transude  under  two  circum- 
stances :  Firstly,  when  the  blood  is  healthy,  the  tissues  being 
then  consequently  healthy ;  secondly,  when  there  is  neither 
undue  delay  nor  undue  pressure  in  the  capillaries  (we  know 
that  albuminoids  will  traverse  animal  membranes  under  undue 
pressure)  ;  conversely  albumen  will  pass  through  the  glomerular 
epithelium  and  the  Malpighian  capsule  under  the  opposite  con- 
ditions. Otherwise  it  seems  to  me  that  we  should  simply  regard 
this  as  one  of  the  ultimate  facts  of  the  organism — as  constituting 


20 


THE  URINE  IN  HEALTH  AND  DISEASE. 


one  of  the  vital  correlations — for  which  we  have  no  satisfactory 
explanation  to  offer.  Another  difficulty  presented  by  the  theory  of 
filtration  is  the  enormous  quantity  of  liquid  which  must  traverse 
and  be  taken  into  the  blood  in  order  to  furnish  the  proportion  of 
urea  eliminated  in  twenty-four  hours.  Besides,  if  this  theory 
were  correct,  there  ought  to  be  a  parallelism  between  the  quantity 
of  urine  and  the  amount  of  urea  excreted  ;  but  in  certain  cases 
this  does  not  obtain.  In  diminishing,  for  instance,  the  calibre  of 
the  renal  artery,  the  urea  relatively  diminishes  in  the  urine.  In 
fine,  according  to  the  theory  of  Ludwig,  the  transudation  from 
the  capillary  vessels  ought  to  cease  when  the  concentration  of 
the  urine  should  become  equal  to  that  of  the  blood  plasma. 
There  would  be  thus  a  limit  to  the  concentration  of  the  urine, 
and  it  could  never  become  more  concentrated  than  the  blood 
plasma.  Hoppe-Seyler  found,  however,  in  putting  the  urine  and 
the  serum  of  the  blood  of  a  dog  in  an  endosmometer,  that  the 
volume  of  the  urine  augmented  by  withdrawing  water  from  the 
serum  of  the  blood.  It  was  thus  more  concentrated  than  the 
latter.  In  this  case,  however,  any  influence  due  to  the  fibrine  is 
not  taken  into  account.  Ribbert,  in  order  to  determine  whether 
the  urine  secreted  by  the  glomerulus  becomes  concentrated  in  the 
convoluted  tubes  in  rabbits,  extirpated  the  medullary  substance, 
and  found  that  the  amount  of  urine  was  greater.  His  experi- 
ments tended  in  favour  of  the  resorption  theory. 

The  Theory  of  Kuss. — In  some  respects  the  theory  of  Kuss  is 
similar  to  that  of  Ludwig,  only  he  evades  the  difficulty  which  we 
have  just  seen  to  be  presented  by  the  theory  of  Ludwig,  Kuss 
maintaining  that  the  whole  serum  filters  through  the  glomerulus, 
as  in  the  case  of  ordinary  serous  transudation.  Hence,  as  the 
fluid  passes  along  the  convoluted  tubes,  according  to  him,  the 
albumen  is  reabsorbed.  The  urine  then  would  consist  of  serum 
less  albumen.  This  looks  a  particularly  clumsy  operation  on  the 
part  of  nature,  in  all  things  so  conservative  of  material,  of  force, 
and  of  energy.  This  resorption  Kuss  holds  would  be  due  to  the 
vital  activity  of  the  epithelial  cells,  aided  by  the  feeble  pressure 
of  the  blood  in  the  pericanalicular  capillaries.  This  theory  is 
held  to  explain  how  cysts  of  the  kidney,  formed  in  consequence 
of  obliteration  of  the   convoluted   tubes,    are   not   found  to 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  21 

contain  urine,  but  an  albuminous  serous  fluid,  and  how  in  these 
cases,  or  when  the  epithelium  of  the  kidney  is  diseased,  it  is 
unable  to  resorb  the  albumen  and  it  thus  appears  in  the  urine. 
It  has  been  found  that  when  albumen  has  been  injected  into  the 
blood  of  rabbits  it  is  eliminated  by  the  glomerulus,  and  that  the 
same  thing  happens  after  temporary  ligature  of  the  renal  artery. 
It  must  be  borne  in  mind  that  here  we  are  dealing  with  a  patho- 
logical condition,  and  that  we  must  not  too  hastily  draw  conclu- 
sions from  such  data  as  to  normal  states  and  functions.  It  is 
thus  evident  that  all  the  three  theories — the  three  most  usually 
accepted — present  difficulties. 

Pressure  of  blood  is  the  main  factor  in  determining  the 
amount  of  the  urinary  secretion.  In  order  that  this  secretion 
take  place,  the  pressure,  it  is  obvious,  must  be  greater  than  the 
pressure  in  the  convoluted  tubes.  It  is  thus  the  difference 
between  the  two  pressures,  and  the  excess  of  the  former  over  the 
latter,  which  determines  the  secretion.  When  this  difference  of 
pressure  is  diminished  or  equalized,  either  by  diminishing  the 
blood-pressure  by  section  of  the  cord,  or  by  copious  bleeding,  or 
by  augmenting  the  pressure  in  the  canaliculi,  as  when  the 
ureter  is  ligatured,  the  secretion  of  urine  diminishes  or  is  totally 
arrested.  The  inverse  result  is  produced  when  the  difference  is 
increased,  as  when  the  blood-pressure  is  experimentally  aug- 
mented by  ligature  of  the  aorta  below  the  renal  artery,  the 
injection  of  water  into  the  blood,  and  contraction  of  the  cutaneous 
vessels,  as  from  cold,  etc.  The  pressure  in  the  renal  artery 
amounts  to  120  to  130  millimetres  of  mercury. 

All  causes  which  influence  the  pressure  of  blood  in  the  renal 
artery  act  indirectly  on  the  urinary  secretion.  Thus,  the  quantity 
of  urine  is  augmented  simply  by  increased  cardiac  activity,  and 
by  diminution  of  the  total  vascular  area,  by  an  augmented 
amount  of  blood,  as  from  large  draughts  of  water,  injection  of 
water  into  the  veins,  etc.  The  secretion  is  diminished  by 
opposite  causes,  such  as  diminution  of  the  activity  of  the  heart, 
excitation  of  the  pneumogastric,  the  action  of  heat  upon  the 
skin,  copious  sweating,  etc.  Augmentation  of  blood-pressure 
not  only  raises  the  amount  of  urine,  but  it  likewise  increases  the 
amount  of  solid  constituents  of  the  urine,  though  in  feebler  pro- 


22  THE  URINE  IN  HEALTH  AND  DISEASE. 

portion.  According  to  Heidenhain,  and  in  this  he  is  supported 
by  Paneth  and  Munck,  the  augmented  pressure  acts  by  acceler- 
ating the  passage  of  blood  through  the  glomerulus. 

Epitome  of  the  Relation  between  Urinary  Secretion  and 
Arterial  Pressure.* 

A.  Secretion  of  urine  may  be  increased  : 

(a)  By  increase  of  the  general  blood-pressure — by 

(1)  Increase  of  the  force  or  frequency  of  heart- 

beat (digitalis,  alcohol,  etc.), 

(2)  Constriction  of  the  small  arteries  in  other 

areas  than  that  of  the  kidney  (skin  from 
cold,  etc.). 

(b)  By  increasing  the  local  blood-pressure,  by  relaxa- 

tion of  the  renal  artery  ivithout  compensating 
relaxation  elseivhere : 

(1)  Division  of  the  renal  nerves  (causing  poly- 

uria). 

(2)  Division  of  the  renal  nerves  and  stimulation 

of  the  cord  below  the  medulla  (causing 
greater  polyuria). 

(3)  Division  of  the  splanchnic  nerves.    As  these 

nerves  are  distributed  to  other  regions, 
other  vessels  are  dilated  besides  the  renal 
artery,  and  the  polyuria  is  consequently 
less  than  in  1  and  2. 

(4)  Puncture  of  the  floor  of  the  fourth  ventricle, 

or  mechanical  irritation  of  the  superior 
cervical  ganglion  of  the  sympathetic.  The 
renal  arteries  are  thus  dilated. 

B.  Secretion  of  urine  may  be  diminished  : 

(a)  By  diminishing  the  blood-pressure — by 

(1)  Diminution  of  the  force  or  frequency  of  the 

heart-beats. 

(2)  Dilatation  of  vessels  in  other  areas  than  the 

kidney  (skin  in  hot  weather). 

*  Kirkes'  'Physiology.' 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY. 


23 


(3)  Division  of  the  cord  below  the  medulla, 
causing  vascular  dilatation  of  the  abdo- 
minal area  and  suppression  of  urine. 

(b)  By  increasing  the  blood-pressure  by  stimulation  of 

the  spinal  cord  below  the  medulla,  when  the 
constriction  of  the  renal  artery  is  not  com- 
pensated for  by  general  increase  of  the  blood- 
pressure. 

(c)  By  constriction  of  the  renal  artery,  by  stimulating 

the  renal  or  splanchnic  nerves  or  the  spinal  cord. 

The  condition  of  the  blood  exercises  a  not  less  marked  influ- 
ence on  the  secretion  of  urine.  In  the  normal  condition  the 
composition  of  blood  oscillates  within  a  certain  range.  Whenever 
this  range  is  exceeded,  that  is  to  say,  whenever  any  constituent  is 
found  in  excess  in  the  blood,  even  if  it  be  a  normal  constituent, 
such  principle  is  eliminated  by  the  kidney,  though  not  normally 
so  eliminated.  Thus,  if  an  excess  of  albumen  be  taken  into  the 
blood,  as  may  happen  from  an  excessive  indulgence,  for  instance, 
in  raw  eggs,  albumen  is  found  in  the  urine.  What  I  have  been 
in  the  habit  of  terming  the  vital  correlation  is  disturbed,  and 
qua  this  a  pathological  state  is  induced.  If  the  theory  of  Kuss 
be  the  correct  one,  it  is  difficult  to  see  why  the  albumen  in  this 
case  is  not  absorbed  by  the  epithelium  of  the  convoluted  tubes. 
It  is  in  this  manner  that  draughts  of  water  augment  the  watery 
portion  of  the  urine,  the  specific  gravity  of  the  blood  being 
restored  to  its  normal  equipoise.  Similarly,  chloride  of  sodium, 
phosphate  of  soda,  and  most  other  salines,  thus  appear  in  the 
urine  in  proportion  to  the  dose  administered.  Glycosuria  shows 
itself  when  the  glycose  exceeds  0*6  per  100  in  the  blood.  Finally, 
all  diffusible  substances  introduced  into  the  organism  rapidly  pass 
into  the  urine.  As  the  nature  of  the  urine  thus  depends  on 
alimentation,  why  the  secretion  of  herbivora  and  carnivora  is 
different,  and  how,  is  apparent.  The  urine  is  thus  a  depuratory 
and  antitoxic  secretion.  Hence,  when  nephrectomy  or  ligature 
of  the  ureter  is  practised,  toxic  manifestations  appear  more 
rapidly ;  and,  conversely,  when  the  urinary  secretion  is  active, 
poisonous  manifestations  are  retarded  and  mitigated.    When  the 


24 


THE  UEINE  IN  HEALTH  AND  DISEASE. 


urinary  passages  eliminate  the  poison  to  the  extent  that  it  is 
ingested,  toxic  phenomena  do  not  appear  at  all.  This  happens, 
according  to  Bernard  and  Hermann,  when  curara  is  introduced 
into  the  stomach.  The  role  of  cellular  activity  on  the  secretion 
of  urine  is  undoubted,  as  shown  by  experiments,  and  especially  by 
artificial  stimulation  of  the  kidney.  If  the  urinary  secretion  be 
arrested  by  diminishing  the  blood-pressure  by  section  of  the 
cord,  or  by  retarding  the  venous  circulation  of  the  kidney, 
secretion  may  be  re-established  by  the  employment  of  certain 
diuretics,  such  as  acetate  of  soda,  urea,  etc.  Abeles  found  that 
when  he  added  to  the  blood  of  the  kidney  blood  unmixed  with 
urea,  not  a  drop  of  blood  flowed  from  the  ureter ;  but  when  he 
added  blood  to  which  urea  had  been  added,  the  blood  flowed 
more  quickly,  and  urine  was  secreted.  Abeles  therefore  infers 
that  urea  paralyzes  the  vaso-constrictor  nerves,  and  excites  the 
vaso-dilators  of  the  kidney  ;  but  the  subsequent  experiments  of 
Munck  and  Phillips  seem  to  demonstrate  that  the  effect  is 
specially  on  the  secretory  cells.  The  influence  of  the  epithelial 
cells  is  further  demonstrated  by  the  mode  of  action  of  the 
different  salts  of  the  urine.  Senator  and  Munck  have  shown 
that  if  the  venous  circulation  of  the  kidney  be  arrested  at  the 
same  time  that  the  quantity  of  urine  diminishes,  the  proportion 
per  cent,  of  urea  diminishes,  while  the  proportion  per  cent,  of 
chloride  of  sodium  does  not  vary.  Lepine  and  Aubert  found 
that  by  temporarily  occluding  the  ureter  of  one  side,  and  com- 
paring the  secretion  of  the  two  kidneys,  that  of  the  side  operated 
on  was  more  concentrated  and  the  phosphates  were  less  perfectly 
eliminated,  but  the  chloride  of  sodium  was  eliminated  as  well  as 
on  the  sound  side. 

Urine  normally  appears  as  a  pale,  straw-coloured  and  trans- 
parent fluid.  It  is  an  excrementitial  liquid,  representing  the 
unutilized  material  introduced  into  the  organism  for  the  purpose 
of  nutrition,  as  well  as  the  products  of  organic  disassimilation. 
The  terms  '  transparency  '  and  '  aspect '  of  urine  are  often  con- 
founded. '  Aspect '  obviously  refers  to  the  naked-eye  appear- 
ance, and  '  transparency  '  to  transmissibility  of  light. 

Transparency. — When  passed,  normal  urine  is  usually  clear 
and  transparent.    After  a  period  of  repose  flakes  of  mucus 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  25 

often  appear,  which,  according  to  the  density  of  the  urine, 
either  remain  suspended  in  the  fluid  or  are  deposited.  This 
mucus  in  the  normal  condition  scarcely  affects  the  transparency 
of  the  urine,  but  in  certain  affections  of  the  urinary  organs  its 
amount  may  be  so  great  as  to  render  the  urine  opaque.  This 
mucus  is  composed  of  epithelial  debris  from  the  bladder,  the 
ureters,  and  the  pelvis  of  the  kidney.  Frequently  the  urine 
becomes  turbid  when  exposed  to  a  low  temperature,  owing  to 
the  precipitation  of  bodies  normally  held  in  solution  at  a  higher 
temperature.  Again,  loss  of  transparency  may  be  due  to  the 
presence  of  adventitious  chemical  compounds  only  found  in  a 
pathological  state,  such  as  earthy  phosphates  of  calcium  and 
magnesium  (in  abnormal  amount),  and  such  constituents  as 
pus  and  chyle. 

Odour. — In  the  normal  condition  fresh  urine  has  a  peculiar 
aromatic  odour.  The  smell  of  urine  is  said  to  be  due  to  the 
presence  of  phenylic,  taurylic  and  damoluric  acids.  The  urine  in 
diabetes  has  a  sweetish,  hay-like  smell.  Urine  containing  cystin 
has  a  smell  similar  to  that  of  sweetbriar,  which  afterwards 
becomes  very  disagreeable.  Certain  medicaments  impart  their 
odour  to  the  urine,  such  as  turpentine  (which  imparts  to  it  the 
smell  of  sweet-violets),  copaiba,  cubebs,  oil  of  santal-wood, 
asparagus  and  garlic.  When  the  urine  contains  decomposing 
blood  or  pus  it  has  a  putrid  odour ;  and  when  it  has  undergone 
decomposition  in  the  bladder  it  exhales  an  ammoniacal  odour, 
and  sometimes  gives  off  sulphuretted  hydrogen. 

Colour. — The  colour  of  urine  varies  according  to  concentra- 
tion or  dilution,  to  the  presence  of  pathological  pigments 
and  to  variations  in  dieting.  It  usually  ranges  from  a  pale 
straw-colour  to  a  reddish  yellow.  The  morning  urine,  which 
is  called  the  urina  sanguinis,  is  of  a  deeper  colour  than  that 
emitted  during  the  day  or  after  the  injection  of  large  draughts 
of  water — the  urina  potus.  Occupying  an  intermediate  place 
between  these  two  in  respect  of  colour,  we  have  the  urine 
evacuated  some  time  after  a  repast — the  urina  chyli.  The 
urine  of  the  infant  is  generally  paler  than  that  of  the  adult,  and 
during  the  first  hours  of  existence  it  is  entirely  colourless.  In 
acute  febrile  maladies,  the  colour  of  the  urine  is  intensely  deep, 


26 


THE  URINE  IN  HEALTH  AND  DISEASE. 


varying  from  a  deep  yellow  to  the  reddish-brown  colour  observed 
in  certain  chronic  affections.  In  diabetes,  hysteria,  anaemia,  and 
granular  kidney,  it  is  usually  pale.  Here  there  is  polyuria  ;  and 
in  the  case  of  the  granular  kidney  the  urine  is  of  low  specific 
gravity,  as  the  convoluted  tubes  are  to  so  great  an  extent 
denuded  of  their  epithelium,  and  the  chief  constituents  of  the 
urine  are  consequently  not  eliminated  (Black's  '  Lectures  on 
Bright' s  Disease,'  p.  82).  In  nervous  affections  the  urine  is 
frequently  colourless  (urina  spastica).  In  affections  of  the 
liver  and  biliary  passages,  the  presence  of  bile  pigments  in  the 
urine  occasions  a  yellowish-green  or  brownish-green  colour 
(icteric  urine).  It  may  also  be  observed  that  in  being  thus 
eliminated  the  bile  pigments  set  up  so  much  irritation  as  to  cause 
the  appearance  of  yellowish  tube-casts  in  the  urine.  The  pre- 
sence of  blood  gives  to  the  urine  a  more  or  less  intense  red  colour, 
as  we  find  it  in  the  early  stages  of  acute  nephritis,  calculous 
nephritis,  cancer  of  the  bladder,  etc.  In  the  condition  termed 
hemoglobinuria,  haemoglobin  exists  in  the  urine,  which  is  thus 
coloured  red.  In  certain  cases  of  melanotic  cancer  the  urine  is 
coloured  black.  Certain  medicaments  alter  its  colour.  Thus, 
santonin,  rhubarb  (crysophanic  acid)  and  senna  impart  to  it  a 
yellowish  colour.  Saffron  causes  it  to  become  of  a  greenish 
colour.  The  coloration  caused  by  the  pigments  of  senna  and 
of  rhubarb  is  not  unlike  that  occasioned  by  the  presence  of  blood, 
but  it  is  easy  to  establish  the  distinction.  The  urine  coloured  by 
the  former  becomes  more  limpid  and  clearer  in  contact  with  a 
mineral  acid,  while  that  by  the  latter  does  not  become  clearer, 
but  rather  becomes  of  a  deeper  colour.  Further,  urine  containing 
pigments  of  rhubarb  and  of  senna  give  with  ammonia  or  with 
potash  a  purple  colour.  The  yellowish  coloration  due  to  san- 
tonin oscillates  from  yellowish-red  to  a  reddish-purple  in  pre- 
sence of  an  alkali. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  27 


Krukenberg  gives  the  following  table  as  to  urine  colours  : 
Pathological  and  other  Urine  Colours. 


Colour  of  Urine. 

Cause  of  Colora- 
tion. 

Pathological  Con- 
dition. 

Pa'e  yellow  to  colour- 
less. 

Diminution  of  normal 
pigments. 

Anaemia,  chlorosis,  dia- 
betes, and  other  ner- 
vous attacks. 

Dark  yellow  to  brown 
red,  easily  deposit- 
ing a  sediment. 

Increase  of  normal  or 
occurrence  of  patho- 
logical pigments. 

Acute  febrile  diseases. 

Yellowish  and  milky. 

Fatty  drops  floating 
in  urine. 

Chyluria. 

Suspended    pus  cor- 
puscle?. 

Pyelitis,  or  other  puru- 
lent disease. 

Green,  or  yellow  green. 

Bile-colouring  matter. 

Jaundice. 

Greenish-yellow;  later 
greenish -brown,  or 
approaching  black. 

Decomposed  haemo- 
globin and  various 
chromogens.  Car 
bolic  acid  urine  is 
similar. 

Haemorrhage  into  the 
kidneys  in  long-con- 
tinued intermittent 
fever ;  also  melano- 
tic cancer. 

Red  or  reddish. 

Unchanged  haemoglo- 
bin. 

Haemorrhage,  or  hae- 
moglobinuria. 

Pigments   which   are   taken   up   with  the 
food,  such  as  madder,  bilberries,  logwood, 
fuchsin,  etc. 

Brown.                        Bile- colouring  matters  and  methaemoglobin. 

Brown-yellow  to  red-  Substances  which  are  introduced  into  the 
brown,      becoming     organism  with  senna,  rhubarb,  chelidonium, 
blood-red  on  adding  etc. 
alkalies. 

Fluorescence,  Temperature,  etc. — Normal  urine  is  slightly 
fluorescent.  With  pale  urine  the  fluorescence  is  bluish ;  with 
reddish-yellow  it  is  green  or  yellow.  Albuminous  urine  is  more 
fluorescent  than  normal  urine,  and  urine  which  has  become 


*  Grundriss  d.  Med.  Chem.  Analyse,  1884,  S.  78. 


28 


THE  URINE  IN  HEALTH  AND  DISEASE. 


alkaline  more  than  undecomposed  urine.  All  normal  urines 
cause  a  right  deviation  of  the  plane  of  polarization.  When  the 
urine  is  albuminous  the  deviation  is  to  the  left.  Saccharine 
urines  cause  a  right:handed  deviation  proportionate  to  the 
quantity  of  sugar. 

When  the  urine  is  agitated,  a  froth  appears  which  rapidly  dis- 
appears on  repose.  With  albuminous  and  saccharine  urines  the 
froth  is  more  abundant  and  disappears  more  slowly.  The 
normal  temperature  of  urine  is  about  37°  C. ;  but  in  certain 
acute  affections,  such  as  pneumonia,  scarlatina,  rheumatism,  etc., 
the  temperature  rises  correspondingly  with  that  of  the  body.  In 
cases  of  idiopathic  tetanus,  it  may  rise  as  high  as  44°  C,  and  fall 
as  low  as  26°  C.  in  cases  of  tubercular  meningitis. 

According  to  Feltz,  Eitter,  Bouchard,  etc.,  normal  urine  is 
toxic.  If  from  90  to  100  grammes  be  injected  into  the  veins  of  a 
rabbit  weighing  2  kilogrammes,  the  animal  is  poisoned  by  lower- 
ing of  its  temperature.  The  toxicity  of  the  urine  depends  on 
various  circumstances  ;  for  example,  cerebral  activity,  muscular 
activity,  sleep,  alimentation,  etc.  Pathological  urines  are  not 
necessarily  more  toxic  than  the  normal.  They  may  even  be  less 
toxic.  In  nephritis  the  urine  is  not  more  toxic  than  distilled 
water,  a  circumstance  doubtless  due  to  the  very  small  amount 
of  urinary  constituents  contained  in  the  urine,  especially  in  that 
of  the  granular  kidney. 

Quantity  of  Urine.  —  The  amount  of  urine  secreted  in 
twenty-four  hours  averages  in  a  healthy  male  individual  from 
1,400  to  1,500  c.c.,°  or  from  49  to  50  ounces.  In  the 
female  the  volume  is  less.  It  oscillates  between  1,000  and 
1,200  c.c.  For  obvious  reasons,  the  amount  is  diminished  when 
the  skin  is  active,  and  vice-versa.  Contraction  of  the  cutaneous 
vessels,  as  from  cold,  etc.,  stimulates  and  augments  the  secretion 
of  urine.  The  smallest  amount  is  secreted  between  2  a.m.  and 
4  a.m.,  and  the  greatest  between  2  p.m.  and  4  p.m.  If  the 
average  quantity  of  urine  secreted  be  compared  with  the  weight 
of  the  body,  we  find  that  for  each  kilogramme  there  is  eliminated, 
on  an  average,  1  c.c.  of  urine  per  hour.  In  the  aged  the 
volume  is  less.     The  quantity  secreted  by  the  infant  at  the 

*  100  c.c.  —  3 \  ounces. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  29 

breast,  compared  with  its  body-weight,  is  three  or  four  times 
greater  than  in  the  case  of  the  adult. 

As  a  rule,  the  largest  amount  of  urine  is  eliminated  about  two 
hours  after  a  repast,  the  least  during  the  night,  and  the  medium 
amount  in  the  morning.  The  secretion  is  augmented  by 
abundant  draughts,  such  as  of  ordinary  water,  beer,  coffee,  and 
water  holding  salines  in  solution.  If  after  large  draughts  of 
water  violent  exercise  be  indulged  in,  the  augmentation  of  the 
volume  of  the  urine  is  less,  as  much  of  the  fluid  is  eliminated  by 
cutaneous  transpiration.  During  winter,  when  the  pulmonary 
and  cutaneous  exhalations  are  much  less  abundant  than  in 
summer,  a  greater  quantity  of  urine  is  secreted  and  vice-versa. 
Excitable  individuals  secrete  more  urine,  and  in  most  people 
nervous  excitement  is  attended  with  increased  micturition.  The 
urinary  secretion  is  less  when  the  amount  of  fluids  ingested  is 
diminished.  After  parturition,  when  the  secretion  of  milk  com- 
mences, the  quantity  of  urine  secreted  diminishes. 

Hydruria  and  Polyuria.  —  Under  certain  circumstances 
patients  pass  from  10  to  12  litres  of  urine  in  twenty-four  hours. 
There  then  exists  polyuria,  and  of  this  state  two  varieties  are 
recognised  : 

First,  Polyuria  properly  so  called,  which  is  divided  into  saccha- 
rine or  diabetic  polyuria,  and  the  polyuria  of  diabetes  insipidus, 
when  there  is  no  sugar  in  the  urine. 

Second,  Simple  Hydruria. 

In  the  first  case,  the  percentage  of  solid  matters  to  the  litre  of 
urine  is  either  normal,  or  sometimes  augmented.  In  the  second 
case  the  fluid  matters  are  almost  normal  in  relation  to  the 
amount  passed  in  twenty-four  hours,  while  feeble  in  proportion  to 
the  litre.  In  this  case  there  is  no  hypersecretion  of  solid  matters, 
but  there  is  a  dilution  of  them  by  the  abnormal  amount  of  water. 
Certain  medicinal  agents  exercise  a  marked  influence  over  the 
urinary  secretion.  The  diuretics  markedly  augment  the  secre- 
tion, and  of  these  the  most  important  are  alcohol,  nitrous  ether, 
nitrate  and  acetate  of  potash,  squills,  digitalis,  broom,  caffeine, 
etc.  Certain  other  medicines  diminish  the  urinary  secretion, 
such  as  opium  (and  especially  its  alkaloid,  codeia),  belladonna, 
salts  of  iron  and  copper  (especially  the  citrate  of  iron  with 


30 


THE  URINE  IN  HEALTH  AND  DISEASE. 


quinine),  ammonia-citrate  of  iron,  etc.  Cantharides  and  arsenic 
may  entirely  suppress  the  urinary  secretion. 

Pathological  States  influence  the  quantity  of  urine.  In  acute 
febrile  affections,  as  in  pneumonia,  pleurisy,  typhoid  fever,  and 
acute  muscular  rheumatism,  the  quantity  is  markedly  diminished ; 
it  then  augments  as  the  intensity  of  the  disease  diminishes,  and 
during  convalescence  it  becomes  normal,  and  sometimes  greater 
in  quantity  than  in  health.  In  cases  of  anaemia,  profuse  loss 
of  blood,  and  in  cholera  the  quantity  is  very  much  diminished. 
In  cholera  the  diminution  frequently  amounts  almost  to  anuria 9 
and  this  condition  may  continue  for  days,  to  be  followed  by 
polyuria.  The  urine  is  likewise  diminished  in  dropsies,  gout, 
and  atrophic  cirrhosis  of  the  liver.  In  the  various  forms  of 
diabetes,  as  from  glycosuria,  phosphaturia,  etc.,  the  quantity  of 
urine  is  always  augmented. 

Variations  of  Density  and  of  Solid  Residue  in  Disease. — 
In  most  acute  and  chronic  diseases,  both  the  density  of  the  urine 
and  the  amount  of  solid  residue  undergo  great  variations,  which, 
from  the  point  of  view  of  diagnosis,  are  of  primary  importance. 
In  the  majority  of  acute  affections  the  urine  passed  is  markedly 
concentrated,  sometimes  attaining  to  a  density  of  1035.  This  is 
chiefly  due  to  the  augmented  excretion  of  urea,  sulphates,  and 
alkaline  phosphates.  We  find  the  same  condition  in  chronic 
affections,  where  there  is  disturbance  of  normal  metamorphosis,, 
as  in  diabetes,  gout,  etc.  In  diabetes  the  urine  may  attain  a 
density  of  1050. 

In  certain  forms  of  Bright's  disease*  (the  cirrhotic  kidney),, 
and  in  the  amyloid  forms  of  kidney  disease,  the  specific  gravity 
of  the  urine  is  very  low.  It  sometimes  descends  to  a  specific 
gravity  of  1005,  or  1004.  The  excretion  of  urea  is  here 
diminished,  owing  to  desquamation  of  the  cells  of  the  convoluted 
tubes.  The  specific  gravity  is  also  diminished  in  cases  of  poly- 
uria and  simple  hydruria,  and  likewise  in  most  nervous  affections 
attended  with  excitement. 

The  Specific  Gravity  of  the  urine  in  the  normal  state  ranges 
from  1015  to  1025.    After  excessive  draughts  of  water  it  has 

*  Vide  'Lectures  on  Bright's  Disease,'  by  Aut!  or.  J.  and  A.. 
Churchill,  London. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  31 


been  known  to  sink  as  low  as  1002  ;  and  according  to  Dr.  W. 
G.  Smith,  it  has  risen  after  great  sweating  and  forced  marches 
from  1035  to  1040.  The  specific  gravity  in  infants  is  as  low  as 
from  1003  to  1006.  The  average  normal  density  may  be  taken 
as  1020.  The  average  density  in  the  female  is  somewhat  less. 
It  may  be  regarded  as  1016.  The  density  varies  with  the 
time  of  the  day,  and  the  nature  of  the  alimentary  substances 
ingested,  muscular  activity,  etc.  A  healthy  adult  male  excretes 
about  70  grammes,  or  2^  ounces,  of  solids  in  his  urine  per  diem. 
Determination  of  the  Density  of  Urine.  —  In  practice 
the  determination  of  the  density  of  urine  is  determined  by 
means  of  the  urinometer.  This  instrument  is  so  graduated 
as  to  indicate  to  half  a  degree  a  density  varying  from  1000, 
that  of  water,  to  1040,  beyond  which  the  density  of  urine  rarely 
passes.  Urinometer s  are  generally  graduated  for  a  temperature 
of  15°  C.  Where  absolute  accuracy  is  necessary,  the  urine 
must  be  of  this  temperature.  If  the  urine  be  in  quantity  in- 
sufficient for  the  employment  of  the  urinometer,  the  specific 
gravity  may  be  obtained  by  weighing  by  means  of  a  small  flask, 
the  picnometer.  Let  P  be  the  weight  of  a  given  volume  of 
urine,  and_£?  the  weight  of  an  equal  volume  of  distilled  water  at 
the  same  temperature  ;  then  P  divided  by  p  will  give  the  density 
of  the  urine. 

P  Weight  of  urine. 
~~  p  Weight  of  water. 

By  means  of  the  hydrostatic  balance  of  Mohr  the  specific 
gravity  may  be  obtained  with  greater  precision  and  rapidity. 

Estimation  of  the  Total  Solids  of  the  Urine. — An  approxi- 
mate to  the  total  solids  of  the  urine  may  be  obtained  by  means  of 
what  is  known  in  this  country  as  Christison's  formula,  and 
abroad  as  that  of  Haeser  or  Trapp.  If  the  last  two  figures  of  the 
specific  gravity  as  expressed  in  four  figures  be  multiplied  by  2*33 
(Christison  and  Haeser),  or  by  2  (Trapp),  the  result  will  give  in 
grammes  the  total  solids  in  1,000  c.c.  The  weight  of  the  solid 
residue  of  the  urine,  or  the  amount  of  solids  which  the  mine 
holds  in  solution,  averages  47  grammes  per  litre  in  a  healthy 
man,  and  37  in  the  female.    This  residue  is  composed  of  organic 


32 


THE  URINE  IN  HEALTH  AND  DISEASE 


and  mineral  substances.  The  former  always  exist,  in  the  normal 
condition,  in  greatest  abundance.  In  order  accurately  to  deter- 
mine the  amount  of  these  solids,  10  c.c.  to  15  c.c.  of  urine  are 
ni3asured  by  means  of  a  pipette,  and  are  allowed  to  flow  into 
a  glass  vessel,  which  is  to  be  hermetically  sealed,  and  whose 
weight  has  been  previously  determined.  The  capsule  is  then 
heated  to  desiccation.  The  capsule  and  contents  are  now 
weighed,  after  having  been  allowed  to  cool,  in  juxtaposition  to 
sulphuric  acid,  under  a  glass  shade.  From  the  weight  thus 
obtained  that  of  the  capsule  is  deducted,  and  the  weight  of  the 
dry  residue  is  then  determined. 

This  procedure,  however,  does  not  give  absolutely  accurate 
results,  for  in  the  process  of  evaporation  at  100°  C,  and  desicca- 
tion at  105°  C,  a  certain  amount  of  ammonia  resulting  from  the 
decomposition  of  urea  is  given  off.  In  order  to  obviate  this,  from 
1  to  2  grammes  of  urine  are  to  be  weighed  between  two  watch- 
glasses.  The  upper  one  is  then  removed,  and  the  lower  one,  con- 
taining the  urine,  is  placed  in  a  vacuum  in  presence  of  sulphuric 
acid.  After  the  space  of  twenty-four  hours,  a  new  weighing  is 
made  to  determine  the  exact  amount  of  the  solid  residue.  If  it  is 
desired  to  determine  separately  the  proportion  of  mineral  sub- 
stances as  apart  from  the  proportion  of  organic  substances  con- 
tained in  the  residue  of  the  urine,  it  suffices  to  destroy  the  latter 
by  incineration.  In  this  case  a  platinum  crucible  must  be  em- 
ployed, and  careful  weighing  be  resorted  to. 

Reaction  of  Normal  Urine. — Normal  urine  always  possesses 
an  acid  reaction.  It  reddens  blue  litmus.  This  reaction  is 
only  rarely  due  to  the  presence  of  a  free  acid.  It  ought  rather 
in  most  instances  to  be  attributed  to  acid  phosphate  of  soda.  It 
may,  however,  be  occasionally  due  to  combinations  of  uric, 
hippuric,  and  lactic  acids.  In  the  normal  condition  the  degree 
of  acidity  is  not  uniform.  The  urine  secreted  during  the  night 
is  more  acid ;  that  passed  after  a  meal  is  less  acid.  Milk  diet 
and  alcoholic  beverages  augment  the  acidity,  and  vegetable  diet 
and  abstinence  diminish  it. 

Determination  of  the  Degree  of  Acidity. — The  degree  of 
acidity  of  urine  is  determined  by  comparing  the  saturating 
power  of  urine  with  that  of  an  acid,  such  as  oxalic  acid.  With 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  33 

this  view  we  find  out  how  much  of  the  latter  corresponds  to  the 
non- saturated  acid  contained  in  a  measured  quantity  of  urine  by 
neutralizing  it  with  an  alkaline  solution,  of  which  each  cubic 
centimetre  represents  a  determined  quantity  of  oxalic  acid.  An 
alkaline  solution  of  caustic  soda  is  employed  so  diluted  that  each 
c.c.  corresponds  to  10  milligrammes  of  oxalic  acid.  The  acid 
solution  is  prepared  by  dissolving  1  gramme  of  non-effloresced 
pure  oxalic  acid  in  100  c.c.  of  distilled  water.  Hence  is  obtained 
a  liquor  containing  in  each  c.c.  10  milligrammes  of  oxalic  acid. 
Of  a  given  specimen  of  urine  to  be  tested,  100  c.c.  are  placed  in  a 
glass  vessel,  and  by  means  of  a  burette  the  soda  solution  is  added 
drop  by  drop.  After  the  addition  of  every  demi- cubic  centi- 
metre, the  liquid  is  stirred  with  a  glass  rod,  and  one  drop  of  the 
solution  is  then  removed  and  placed  on  a  piece  of  blue  litmus 
paper.  If  the  reaction  is  still  acid,  as  manifested  by  a  reddening 
of  the  paper,  the  soda  solution  is  added  until  this  reaction  is  no 
longer  produced.  The  number  of  c.c.  of  the  soda  solution 
necessary  to  neutralize  the  urine  is  then  noted.  It  is  thus  eas}- 
to  calculate  how  much  oxalic  acid  corresponds  to  the  acidity  of 
100  c.c.  of  the  urine,  for  we  know  that  1  c.c.  of  the  soda  solution 
corresponds  to  10  milligrammes  of  oxalic  acid.  If,  for  example, 
12  c.c.  of  the  soda  solution  were  required  to  neutralize  100  c.c. 
of  the  urine ;  then  *010  x  12  =  0'12  grammes  of  oxalic  acid.  Other- 
wise, the  estimation  of  the  acidity  of  the  urine  may  be  obtained 
by  means  of  this  standard  solution,  and  a  solution  of  phenol- 
phthalein,  by  which  the  point  of  neutralization  is  indicated. 
Phenol-phthalein,  one  of  the  coal-tar  products,  is  devoid  of 
colour  in  the  acid  and  neutral  states,  but  becomes  of  a  deep 
magenta  colour  in  presence  of  an  alkali.  The  standard  solution 
of  soda  is  the  normal  volumetric  solution  of  the  British  Pharma- 
copoeia, of  which  100  c.c.  are  made  up  to  a  litre.  The  litre 
contains  40  grammes  of  pure  caustic  soda,  and  each  c.c.  of  this 
solution  represents  an  equivalent  of  *0063  grammes  of  crystallized 
oxalic  acid. 

Mode  of  Estimation.— Place  10  c.c.  of  the  urine  to  be 
examined  into  a  porcelain  dish,  and  add  two  or  three  drops  of 
phenol-phthalein  solution.  This  solution  is  made  by  dissolving 
0*2  to  0*3  grammes  in  100  c.c.  of  alcohol.     From  a  10  c.c. 

3 


34 


THE  URINE  IN  HEALTH  AND  DISEASE. 


measure  graduated  to  tenths  of  a  c.c,  drop  into  the  urine  the 
soda  solution,  constantly  stirring,  until  the  permanent  pink 
tinge  has  been  produced,  which  indicates  that  the  acidity  has  been 
overcome.  Eead  off  the  amount  of  the  standard  solution,  each 
c.c.  of  which  corresponds  to  *0063  grammes  of  crystallized 
oxalic  acid;  then  the  number  of  c.c.  of  the  soda  solution  multi- 
plied by  -0063  will  represent  the  acidity  expressed  as  grammes 
of  crystallized  oxalic  acid  per  10,  and  this  result  multiplied  by 
100  will  represent  the  acidity  per  1,000  of  urine. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY. 


35 


Table  showing'  the  Amount  of  Acidity, 

expressed  as  Oxalic  Acid  in  parts  (by  weight)  per  1,000  (by  volume) 
for  the  number  of  c.c.  of  decinormal  Alkali  required  to  neutralize 
10  c.c.  of  Urine. 


C.  C.  to 
Neutralize 

Oxalic  Acid 

grammes 
per  1,000  c.c. 

C.  C.  to 
Neutralize 

Oxalic  Acid 
grammes 
per  1 ,000  c.c. 

C.  C.  to 
Neutraliza 

Oxalic  Acid 

grammes 
per  1 ,000  c.c. 

o-i 

0-063 

4-6 

2-898 

9-1 

5-733 

0-2 

0'12i 

47 

2-961 

9  2 

5-796 

0-3 

0-189 

4-8 

3-024 

9-3 

5-859 

0'4 

0-252 

4-9 

3-087 

9-4 

5-922 

0-5 

0-315 

5-0 

3-150 

9-5 

5-985 

0-6 

0-378 

5-1 

3-213 

96 

6-048 

07 

0-441 

5  2 

3-276 

9-7 

6-111 

0-8 

0-504 

5-3 

3-339 

9-8 

6-174 

0-9 

0-567 

5-4 

3-402 

9-9 

6-237 

1-0 

0*630 

5-5 

3-465 

io-o 

6-300 

1-1 

0693 

5-6 

3-528 

10-1 

6-363 

1-2 

0-756 

57 

3-591 

102 

6  426 

1-3 

0*819 

5  8 

3-654 

10-3 

6-489 

1-4 

0-882 

5-9 

3-717 

10-4 

6-552 

1-5 

0*946 

6-0 

3-780 

.10-5 

6-615 

1-6 

1-008 

6-1 

3-843 

10-6 

6-678 

17 

1-071 

6-2 

3-906 

10-7 

6-741 

1-8 

1-134 

6-3 

3-969 

10-8 

6-804 

1-9 

1-197 

64 

4-032 

10-9 

6-867 

20 

1-260 

6-5 

4-095 

11-0 

6-930 

2-1 

1  323 

6-6 

4-158 

11-1 

6-993 

2-2 

1-386 

6-7 

4-221 

11-2 

7*056 

2-3 

1-449 

6-8 

4-284 

11-3 

7*119 

2-4 

1-512 

6  9 

4-347 

11-4 

7*182 

2-5 

1-575 

7-0 

4-410 

11-5 

7*245 

2-6 

1-638 

7-1 

4-473 

11-6 

7-308 

27 

1-701 

7-2 

4-536 

11-7 

7-37L 

2-8 

1-764 

7-3 

4-599 

11-8 

7-434 

2-9 

1-827 

7-4 

4-662 

11-9 

7-497 

3-0 

1-890 

7-5 

4-725 

12-0 

7*560 

3-1 

1-953 

7-6 

4-788 

12-1 

7-623 

3-2 

2  016 

7-7 

4-851 

12  2 

-  7-686 

3-3 

2-079 

7-8 

4-914 

12-3 

7-749 

34 

2-142 

7-9 

4-977 

12-4 

7-812 

3  5 

2-205 

8-0 

5-040 

12-5 

7  875 

3-6 

2-268 

8-1 

5-103 

12-6 

7-938 

37 

2-331 

8  2 

5-166 

12-7 

8*001 

3-8 

2-394 

8-3 

5-229 

12-8 

8-064  : 

3-9 

2  457 

8-4 

5-292 

12-9 

8-127 

4-0 

2-520 

8-5 

5-355 

13-0 

8-190 

4-1 

2-583 

8-6 

5-418 

13-1 

8"253  ' 

4-2 

2  646 

8-7 

5-481 

13-2 

8-S16  t 

4-3 

2-709 

8  8 

5-544 

13-3 

8-379 

4-4 

2-772 

8-9 

5-607 

13-4 

8-442 

4-5 

2-S35 

9-0 

5*670 

13-5 

8-505 

36 


THE  URINE  IN  HEALTH  AND  DISEASE. 


Or  let  a  solution  of  oxalic  acid  be  made  containing  6*3  grammes 
per  litre  in  distilled  water.  Put  into  a  glass  vessel  10  c.c.  of  this 
standard  acid  solution,  adding  three  drops  of  an  alcoholic  solution, 
of  phenol-phthalein,  and  determine  the  volume  N  of  a  dilute 
alkaline  solution  of  potash  or  soda  requisite  to  saturate  the  acid 
solution.  The  10  c.c.  of  the  oxalic  acid  solution  contain  63  milli- 
grammes of  oxalic  acid,  or  an  equivalent  of  49  H2S04.  The 
alkaline  solution  is  added  by  means  of  a  graduated  burette.  Kead 
off  the  number  N  of  c.c.  used  to  neutralize  the  acid.  This  being 
ione,  repeat  the  operation,  putting  into  the  glass  vessel  10  c.c. 
of  the  urine,  instead  of  the  acid  solution,  and  having  added  the 
alkaline  solution  until  the  earthy  phosphates  show  a  milkiness, 
add  three  drops  of  phenol-phthalein  solution,  and  then  con- 
tinue the  addition  of  the  alkaline  solution  until  a  persistent 
rose-tint  appears.  Then  read  off  the  number  of  c.c.  of  the 
alkaline  solution  required  to  effect  this  change  ;  hence 
N  :  49  : :  N"  :  x. 

Estimation  of  the  Alkalinity  of  the  Urine. — The  estimate 
of  the  alkalinity  of  the  urine  is  determined  by  its  power  of 
neutralizing  a  solution  of  oxalic  acid,  every  10  c.c.  of 
which  are  equivalent  to  17  milligrammes  of  ammonia.  Place 
10  c.c.  of  the  acid  solution  in  a  glass  jar,  and  from  a  burette 
add  the  urine. 

Variations  in  the  Reaction  of  the  Urine.  —  Certain 
medicinal  agencies  modify  the  reaction  of  the  urine ;  alkalies, 
alkaline  carbonates,  and  vegetable  acids  (converted  in  the  system 
into  carbonates),  render  it  alkaline.  In  typhoid  fever  the  acidity 
is  much  above  the  normal.  It  augments  with  the  intensity  of 
the  fever,  and  diminishes  as  the  fever  disappears,  the  urine  be- 
coming alkaline  during  convalescence.  The  same  thing  obtains 
in  cases  of  pneumonia,  pleurisy,  rheumatism,  etc.  In  diabetes 
and  rickets  there  is  preternatural  acidity.  Mineral  acids,  being 
often  eliminated  without  undergoing  change,  render  the  urine 
acid. 

In  cases  of  general  debility,  chloro-angemia,  and  depressing 
affections  of  the  nervous  system,  the  urine  is  slightly  alkaline. 
When  the  vegetable  acids  are   taken  in  large  quantity,  the 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  37 


earthy  phosphates  may  be  precipitated.  In  this  case  an  alkaline 
reaction  is  imparted  to  reddened  litmus.  This  blue  colour  per- 
sists after  desiccation.  It  is  otherwise,  however,  if  the  alkalinity 
be  due  to  the  decomposition  of  urea,  and  its  transformation  into 
carbonate  of  ammonia.  In  this  case  the  litmus  which  has 
become  blue  becomes  red  if  heated,  owing  to  the  volatilization  of 
carbonate  of  ammonia,  and  a  glass  tube  moistened  with  hydro- 
chloric acid  evolves  white  vapour  if  held  above  the  urine 
(chloride  of  ammonium).  The  alkaline  fermentation  of  urea 
may  take  place  in  the  bladder,  and  then  the  urine  is  alkaline 
when  voided.  It  exhales  a  foetid  odour,  and  usually  contains 
a  deposit  of  pus,  with  crystals  of  triple  phosphates,  urate  of 
ammonia,  and  amorphous  granulations  of  carbonates  and 
phosphates  of  lime  and  magnesium.  In  cases  of  cystitis  and 
paralysis  of  the  bladder  this  is  a  frequent  occurrence.  Urine 
may  be  voided  acid,  and  become  alkaline  on  exposure  to 
air. 

Chemical  Composition  of  the  Urine. — Normal  urine  con- 
tains substances  which,  having  served  their  purposes  in  the 
organism,  fall  to  be  eliminated  as  refuse  products.  Of  these 
substances  the  normal  elements  of  the  urine  comprise  two 
groups,  the  one  formed  of  organic  elements,  which  are  the 
products  of  retrogressive  metamorphosis,  the  other  of  inorganic 
elements.    They  may  be  thus  enumerated  : 

Organic  Elements. — Urea,  creatinine,  creatine,  xanthine,  uric 
acid,  allantoine,  oxaluric  acid,  hippuric  acid,  benzoic  acid,  succinic 
acid,  oxalic  acid,  phenols,  sulphocyanic  acid,  colouring  matters, 
mucine,  and  leucomaines. 

Inorganic  Elements. — Soda,  potash,  lime,  magnesia,  iron, 
combinations  of  hydrochloric,  sulphuric  and  phosphoric  acids, 
phospho-glyceric  acid,  silicic  acid,  ammonia,  nitric  and  nitrous 
acids,  peroxide  of  hydrogen,  carbonic  acid  gas,  oxygen  and 
nitrogen. 

The  elements  of  the  first  group  thus  exist  in  greater  abundance 
than  the  second.  One  kilogramme  of  urine  contains  these 
substances  in  the  following  proportions  : 


33 


THE  URINE  IN  HEALTH  AND  DISEASE. 


organic  elements  ==  32*114  grammes,  consisting  of 

Urea   24*270  grammes. 

Uric  acid      0*400 

Hippuric  acid  ...       ,..       ...  1*000 

Creatinine  and  creatine      ...       ...      1*000  ,, 

Xanthine    0*004  ,, 

Colouring  matter     ...       ...       ...      5*440  ,, 

inorganic  elements  =  15*530  grammes. 

Chloride  of  sodium  ...       ...  ...  10*231  grammes. 

Alkaline  sulphates    ...       ...  ...      3*100  ,, 

Alkaline  phosphates .. .       ...  ...      1*431  ,, 

Alkaline  phosphates  of  magnesia  ...  0*455 

Alkaline  phosphates  of  lime  ...      0*313  ,, 

Toxicity  of  the  Urine. — By  injecting  urine  into  the  veins, 
he  observed  the  following  results :  myosis,  acceleration  of  the 
respiration,  difficulty  of  movement  (akinesis),  somnolency, 
polyuria,  disappearance  of  the  corneal  reflexes,  and  convulsions. 
It  is  not  probable  that  these  results  bear  any  relation  to  the 
amount  of  urine  injected,  for  in  the  case  of  pure  water  122  c.c. 
per  kilogramme  are  required  to  kill  a  rabbit ;  while  the  injection 
of  46  c.c.  of  normal  urine  causes  death.  The  toxicity,  therefore, 
is  in  the  urinary  constituents.  Taking  urea  in  an  isolated  form, 
Bouchard  found  that  the  intravenous  injection  of  6*43  gr.  killed 
a  rabbit.  The  mineral  salts,  and  especially  those  of  ammonia 
and  potash,  are  very  toxic.  They  cause  convulsions.  The 
toxicity  of  the  urine  is  diminished  by  decolorization  with  carbon. 
It  probably  removes  other  constituents  than  pigments.  That 
the  toxicity  of  urine  is  not  due  to  volatile  principles  is  shown  by 
its  persistence  after  boiling.  Bouchard  has  demonstrated  that 
the  matters  soluble  in  water  are  less  toxic  than  those  which  are 
soluble  in  alcohol.  The  latter  cause  coma,  diuresis,  and  abundant 
ptyalism.  The  elements  soluble  in  water  cause  convulsions  and 
myosis.  Urine  secreted  in  the  waking  state  is  more  toxic  than 
that  secreted  during  sleep  ;  the  latter  is  convulsive,  the  former 
narcotic.    According  to  Bouchard,  urcemia  is  a  poisoning  re- 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  39 

suiting  from  all  the  urinary  constituents,  although  in  unequal 
proportions,  accumulating  in  the  blood  through  interrupted 
elimination  by  the  kidney. 

Pathological  Sediments  and  Concretions.— The  proportion 
of  the  normal  constituents  of  the  urine  undergoes  wide  variation 
apart  from  that  due  to  alimentation,  age,  sex,  etc.,  in  certain 
pathological  conditions.  Here  there  are  found  in  the  urine 
elements  which  it  does  not  contain  in  the  normal  state,  and 
which  constitute  an  important  diagnostic  sign.  Of  these  the 
most  important  are  albumen,  and  other  albuminoid  bodies, 
such  as  globulin,  hemialbumose,  haemoglobin,  and  peptones, 
sugars  (especially  glucose),  elements  of  the  bile  (biliary  acids, 
cholesterine,  etc.),  acetone,  tyrosine,  and  leucine,  cystine,  fats, 
etc.  All  the  normal  and  all  the  pathological  elements  are 
usually  found  in  solution  in  the  urine,  but  sometimes  they  are 
precipitated  more  or  less  quickly  after  micturition,  or  even  in  the 
urinary  passages.  The  urine  is  said  then  to  contain  sediments 
whose  examination  should  be  carefully  made.  Sometimes  these 
sediments  are  composed  of  insoluble  pathological  elements, 
which  are  never  found  dissolved  in  the  urine.  When  these 
sediments  form  in  the  urinary  passages,  they  may,  instead  of 
being  eliminated,  increase  by  accretion  in  the  bladder  or  kidney 
and  constitute  calculi. 

Accidental  Elements  of  the  Urine. — The  greater  portion  of 
medicinal  agents,  either  given  as  such  or  as  poisons  with  criminal 
intent,  are  eliminated  by  the  urine,  and  can  be  discovered  there. 
These  constitute  the  accidental  elements  which  are  of  importance 
both  to  the  physician  and  to  the  toxicologist. 


40 


THE   UEINE  IN  HEALTH  AND  DISEASE. 


Eeactions  of  Normal  Urine,  and  Significance. 


r  The  urin  e  is  acid  (acidity 
|  due  usually  to  acid  phos- 
It  reddens  I  phate  of  sodium,  rarely  to 
blue     -I  free  acid).  Occasionally 
litmus,    j  the  acidity  may  be  due  to 
I  acid  combinations  of  uric, 
^hippuric,  and  lactic  acids. 
f    It  evolves  a  gas 
which  lenders  red 
litmus  blue.  The 
deposit  contains 
triple  phosphates 
(ammonio  -  phos- 
phate   of  mag- 
nesia). 


It  ren- 
ders 
red 
litmus 
paper 
blue. 


The  urine 
is 

alkaline. 
-On  being  • 
heated  in 
a  test- 
tube 


It  '  does     not'  The  £r ine 
evolve  gas.     The  alkaline 
deposit    contains  V 

triple    phos-J  T0^-  • 

from  the 
bladder. 


phate. 


The  urine  has  become  ammoniacal 
from  decomposition  of  the  urea 

(3CH4N20  =  H3C3N3O3+  3NH3) 
urea         cyanuric  ammonia 
acid 

'Sufficiently  con-^ 
centra  ted ,  on  be-  Alkalinity 
ing  treated  with      due  to 
an  acid  it  evolves  V  alkaline 
a  gas  which  ren-      carbon - 
ders  lime-water  ates. 
turbid.  J 

~\  Alkalinity 
Treated      simi-      due  to 
larly,  it  does  not  \  alkaline 
evolve  a  gas. 


I  phos- 
J  phates. 

1.  A  little  hydrochloric  acid  added  to  a  large  quantity  of  urine 
(5  c.c.  to  100)  causes  coloured  crystals  of  uric  acid  of  various 
shapes  to  separate  out  after  ten  or  twelve  hours. 

A  large  quantity  of  hydrochloric  acid  added  to  a  little  urine 
(3  to  1)  causes  the  formation  of  indigo  blue  and  indigo  red,  the 
urine  becoming  pale  red,  then  brownish- red,  or  violet  to  deep 
blue.  This  coloration  may  be  due  to  the  oxidation  of  other 
chromogens,  such  as  compounds  of  skatol  and  the  reducing 
substances. 

2.  If  some  urine  be  gently  poured  on  the  surface  of  common 
red  nitric  acid,  a  garnet-red  zone  forms  at  the  surface  of  contact 
(Hiller's  'urophaein'  ring),  which  is  better  seen  against  a  white 
background.  (In  urines  rich  in  uric  acid,  just  over  the  ring  there 
may  be  a  white  layer  caused  by  the  separation  of  urates,  which 
may  be  mistaken  for  albumen.) 

3.  Caustic  soda  as  well  as  ammonia  precipitates  out  the  phos- 
phates of  the  alkaline  earths,  which  separate  partly  in  bunches 
of  long  needle-shaped  crystals,  partly  in  the  amorphous  form. 

4.  Warming  with  phospho-molybdic  acid  causes,  after  acidu- 
lation  with  nitric  acid,  a  lively  blue  coloration,  due  to  its  action 
on  the  urates. 


ANATOMY  AND  PHYSIOLOGY  OF  THE  KIDNEY.  41 


5.  Iodized  starch  is  decomposed  by  urine  (presence  of  H202). 

6.  By  adding  mercuric  nitrate  in  solution  for  some  time  a 
clouding  arises,  which  disappears  on  agitation,  due  to  the  forma- 
tion of  sodium  nitrate  and  perchloride  of  mercury  ([N03]2Hg-f 
2NaCl=2NaN03+HgCl2)  soluble  in  acid  urine.  After  all  the 
chloride  of  sodium  is  decomposed  a  permanent  precipitate  forms, 
due  to  a  combination  of  the  urea  with  a  salt  of  mercury.  (Basis 
of  Liebig's  method  of  estimating  urea.) 

7.  Chloride  of  barium  precipitates  baric  sulphate,  BaS04,  and 
phosphate,  Ba3(P04)2;  when  this  precipitate  is  dissolved  in 
hydrochloric  acid  a  cloudiness  is  left. 

8.  Nitrate  of  silver  precipitates  silver  chloride,  AgCl,  and 
phosphate,  Ag3P04 ;  the  latter  first,  afterwards  all  the  chlorine  in 
the  urine,  combines  with  the  silver. 

9.  Lead  acetate  precipitates  sulphate  of  lead,  PbS04,  phos- 
phate, Pb3(P04)2,  and  chloride,  PbCl2,  besides  other  substances. 

10.  Ferric  chloride  precipitates,  after  previously  acidulating 
with  acetic  acid,  phosphate  of  iron,  Fe2(P04)2. 

11.  An  ammoniacal  solution  of  cupric  oxide  is  decomposed  by 
boiling  by  the  action  of  the  urates. 

12.  Tannic  acid  produces  no  precipitate  with  normal  urine. 
(Krukenberg,  Grundriss  d.  Med.  Chem.  Analyse,  1884.) 


PART  II. 


CHAPTEK  II. 
NORMAL  ELEMENTS  OF  THE  URINE. 

History  of  Urea— Description — Physiological  Conditions  which  modify 
the  Amount  of  Urea  —  Chemistry — Artificial  Production  of  Urea,  etc. 
— Physical  Properties — Combinations  with  Acids — Extraction  and 
Preparation  of  Urea — Quantitative  Analysis  of  Urea — Process  of 
Leconte  —  Process  of  Millon — Process  of  Liebig — Volumetric  Analysis 
—  Hypobromite  Process  —  Pathological  Significance  —  Uraemia  — 
Medicinal  Agents  which  Influence  the  Excretion  of  Urea — Thera- 
peutic Indications. 

The  normal  constituents  of  the  urine  are  divisible  into :  (1)  Or- 
ganic Substances,  (2)  Inorganic  Substances,  and  comprise  the 
following  : 


ORGANIC  SUBSTANCES. 

Urea. 

Uric  acid  (urates). 
Hippuric  acid. 
Creatine  and  creatinine. 
Xanthine  and  hypoxanthine. 
Oxaluric  acid. 
Allantoine. 
Succinic  acid. 
Benzoic  acid. 

Oxalic  acid  (oxalate  of  lime). 
Volatile  acids  (phenols). 
Colouring  matters. 


INORGANIC  SUBSTANCES. 

Chloride  of  sodium. 
,,       of  potassium. 

Sulphuric  acid  and  sulphates. 

Phosphoric  acid  and  phosphates. 

Phosphoglyceric  acid. 

Potash,  soda,  lime,   and  mag- 
nesia. 

Ammoniacal  salts. 

Iron,  silica,  nitrates  and  nitrites. 

Peroxide  of  hydrogen. 

Carbonic     acid,    oxygen  and 
nitrogen. 


NOKMAL  ELEMENTS  OF  THE  URINE. 


43 


Nitrogenous  Constituents  (Organic). 


Urea, 


Percentage 
composition. 


CO(NH2)2 


Carbon  12 

Hydrogen  4 

Nitrogen  28 

Oxy  gen  16 


12x1=12 
1x4=  4 
14  x  2=28 
16x1=16 


20-00 
6-66 
46-67 
26-67 


60  =  comb.  wt. 


100-00 


History. — This  substance,  one  of  the  most  important  con- 
stituents of  the  urine,  was  discovered  by  Boerhaave  prior  to  1720, 
but  it  seems  to  have  attracted  little  attention  until  1771,  when  it 
occurred  to  the  younger  Kouelle  to  extract  with  spirit  of  wine 
the  *  saponaceous  matter  '  or  syrup  obtained  by  the  evaporation 
of  urine.  This  extract  he  found  to  be  crystallizable,  and  con- 
ceived that  it  contained  hydrochloric  acid  as  an  essential  in- 
gredient. Prior  to  this,  Boerhaave  succeeded  in  separating  the 
chloride  of  sodium  and  the  urea.  In  1798  Cruikshank  obtained 
this  principle  in  the  form  of  crystal,  but  it  was  not  until  1799 
that  Fourcroy  and  Vauquelin  obtained  it  in  a  pure  form,  and 
recognised  it  as  the  crystallized  substance  of  Rouelle.  Berzelius 
was  the  first  to  obtain  it  in  a  colourless  form  by  means  of  oxalic 
acid,  and  Prout  ultimately  established  its  composition. 

Description. — Urea  is  one  of  the  products  of  the  perfect  oxida- 
tion of  nitrogenous  tissue  in  the  living  body.  Of  the  solid  con- 
stituents of  the  urine  it  constitutes  one  half,  while  a  fourth  is 
made  up  of  chloride  of  sodium.  It  exists  in  the  urine  of  all  the 
mammifera,  birds,  and  reptiles,  but  it  is  in  the  urine  of  car- 
nivorous animals  that  it  exists  in  greatest  abundance.  It  is 
formed  in  the  blood,  or,  more  strictly  speaking,  it  is  a  product  of 
the  interchange  of  blood  constituents  with  the  nitrogenous 
textures  of  the  body,  and  it  is  simply  filtered  from  the  system  by 
the  kidneys.  This  is  demonstrated  by  the  fact  that  when  struc- 
tural disorganization  of  the  kidney  supervenes  on  disease  (as  in 
Bright's  disease),  urea  and  other  excrementitious  substances 
accumulate  in  the  blood,  and  give  rise  to  the  form  of  blood- 
poisoning  termed  uraemia. 


44 


THE  URINE  IN  HEALTH  AND  DISEASE. 


In  the  serous  effusions  which  attend  diseases  of  the  kidney  and 
in  the  sweat  a  much  larger  quantity  of  urea  is  found  than  in  the 
normal  condition.  In  cholera,  which  is  attended  with  sup- 
pression of  the  urine  and  deficient  oxidation  of  tissue,  urea,  in 
consequence,  is  found  correspondingly  diminished  in  the  blood. 
No  trace  of  urea  is  found  in  the  muscular  tissue  or  juice  of 
muscle,  but  there  are  other  nitrogenous  substances  representing 
a  lower  form  of  oxidation,  such  as  creatine  and  xanthine,  and 
from  which  urea  can  be  produced.  That  such  transformation 
takes  place  in  the  organism  is  shown  when,  by  introducing  such 
substances  as  uric  acid,  allantoine,  and  creatine  into  the  blood, 
the  quantity  of  urea  is  forthwith  augmented  in  the  urine.  This 
transformation  is  effected  by  means  of  the  oxygen  and  the  alkalies 
of  the  blood. 

Besides  existing  normally  in  the  urine  and  in  the  blood  (0*16 
per  1,000,  Picard),  (0*177,  Marchand),  urea  is  found  in  the 
amniotic  fluid,  in  the  chyle,  and  lymph  (2  per  1,000,  Wartz),  in 
the  saliva  (0'36  per  1,000,  Picard ;  0*67  to  1  per  1,000,  Kabuteau).* 

According  to  Eabuteau  and  Papillon,  urea  exists  in  notable 
quantity  in  the  peritoneal  cavity  of  flat  fish  under  the  form  of 
trimethylurea,  which,  they  point  out,  is  decomposed  under  the 
influence  of  alkalies  and  ammonia  into  trimethylamine. 

Alimentation  exercises  a  direct  influence  over  the  amount  of 
urea  excreted  from  the  body ;  for  while  upon  a  mixed  diet 
25  grammes  per  day  may  be  eliminated  (2*5  to  3*2  per  cent.),  the 
quantity  may  be  increased  to  50  grammes  if  a  highly  nitrogenous 
diet  be  indulged  in.  Lehmann  found  the  quantity  to  amount  to 
as  much  as  58  grammes  in  the  twenty-four  hours  on  a  purely 
animal  diet,  and  to  decrease  to  15  grammes  on  a  non-nitro- 
genous diet.  Urea  does  not  disappear  from  the  urine  even  when 
no  food  is  taken.  So  strongly  may  the  urine  become  im- 
pregnated with  urea,  that  the  mere  addition  of  nitric  acid  to  it, 
without  evaporation,  may  determine  the  instant  formation  of 
nitrate  of  urea. 

The  question  has  been  propounded  whether  it  is  necessary 
for  the  production  of  urea  from  nitrogenous  principles  that  they 
be  previously  incorporated  with  the  organism.    It  has  been 
*  Comptes  Itendus  de  la  Socicte  de  Biol.,  1871,  p.  180. 


NORMAL  ELEMENTS  OF  THE  URINE. 


45 


maintained*  that  certain  nitrogenous  principles  of  food  are  con- 
vertible into  urea  by  the  system  without  previous  assimilation, 
just  as  sulphates  and  phosphates  appear  rapidly  in  the  urine 
after  the  ingestion  of  a  diet  rich  in  sulphates  and  phosphates. 
In  this  manner  it  was  concluded  that  a  portion  of  the  urea 
found  in  the  urine  is  directly  traceable  to  the  food. 

This  opinion  must  be  received  with  reservation,  and  for  the 
following  reasons :  Urea  is  formed  by  the  system  even  when 
no  food  whatever  is  taken,  and  its  proportion  diminishes  but 
very  little  during  the  first  days  of  fasting  ;  it  is  notably  increased 
by  muscular  exertion,  and  it  is  with  much  difficulty  artificially 
formed  from  nitrogenous  materials  which  have  been  subjected 
to  the  physiological  processes  of  the  body.  Admitting  that  it 
does  appear  in  augmented  proportion  in  the  urine  after  food,  it 
seems  more  reasonable  to  suppose  that  the  alimentary  principles 
which  find  their  wa}T  into  the  blood  give  a  stimulus  to  the  dis- 
integration and  oxidation  of  tissue,  and  that  there  is  an  accele- 
rated circulation  attendant  on  the  process  of  digestion.  It  seems 
to  me  that  it  is  in  this  relation  that  the  augmented  production 
of  urea  and  alimentation  ought  to  be  regarded. 

In  a  paper  on  this  subject  Dr.  Salkowskif  remarks  that  the 
principal  facts  are  that  certain  amido-acids,  after  their  ingestion 
in  the  alimentary  canal,  appear  in  the  urine  in  the  form  of 
uramid  acids,  or  combinations  of  the  amido-acids  with  the  group 
COXH.  Secondly,  certain  other  amido-acids,  such  as  glycocoll, 
leucin,  asparaginic  acids,  which  are  products  of  the  disintegra- 
tion of  albumen,  when  administered  with  the  food,  lead  to 
augmented  excretion  of  urea,  and  after  the  ingestion  of  sal 
ammoniac  the  greater  part  of  the  nitrogen  appears  in  the  urine 
as  urea. 

Physiological  Conditions  which  modify  the  Amount  of 
Urea. — In  the  condition  of  health,  the  amount  of  urea  in  the  urine 
varies  at  different  periods  of  the  day,  and  with  the  nature  and 
quantity  of  food  and  exercise.  As  we  have  seen,  it  is  augmented 
by  nitrogenous  diet  and  exercise ;  cold  baths  and  intellectual 
activity  (Byasson)  are  alleged  to  have  a  like  influence.  The 
*  Comptes  Rendus  de  la  Socieie  de  Biol.,  1871.  p.  180. 
t  Centralblatt,  No.  53,  1875. 


46 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


quantity  is  diminished  by  repose  and  a  vegetable  diet.  Kabu- 
teau*  has  made  the  interesting  observation  that  during  men- 
struation the  amount  of  urea  is  diminished  by  20  per  cent. 
The  diminution  appears  two  days  before  the  appearance  .of  the 
menses,  and  ceases  a  few  days  afterwards.  During  that  time 
the  pulse  diminishes  in  frequency,  and  the  temperature  is 
lowered  by  about  half  a  degree.  This  is  a  most  interesting 
observation  in  view  of  the  fact  that  while  in  man  the  amount 
of  carbonic  acid  gas  eliminated  as  he  advances  in  life  up  to 
forty  or  fifty  years  of  age  augments,  in  woman,  from  the  estab- 
lishment of  menstruation  to  the  menopause,  the  amount  of 
carbonic  acid  eliminated  by  the  system  is  not  greater  than  in 
the  girl  of  fifteen.  During  twenty  days  of  each  month  the  adult 
female  eliminates  much  more  urea  and  carbonic  acid  than  the 
non-menstruating  girl.  The  female  who  eliminates  from  14  to 
15  grammes  of  urea  during  the  period  of  menstruation  elimi- 
nates from  19  to  20  grammes  before  menstruation  and  five  or 
six  days  after  it  has  ceased.  Now,  physiological  data  show  that 
a  direct  relationship  exists  between  the  quantity  of  blood  dis- 
charged from  the  system  at  this  period  and  the  amount  of 
carbonic  acid  and  urea  formed ;  for,  as  we  know,  the  red- blood 
corpuscles  are  the  carriers  of  oxygen ;  it  is  through  their  agency 
that  the  nervous  centres  are  stimulated,  and  it  is  by  their 
means,  through  their  ox}7gen,  that  eremacausis  is  carried  on, 
and  carbonic  acid  and  urea  produced. 

Generally  speaking,  an  adult  man  eliminates  in  his  urine 
from  18  to  30  grammes  per  day ;  a  female,  on  an  average,  25 
grammes  Some  authorities  give  a  higher  figure.  Neubauer, 
in  the  case  of  an  individual  on  a  mixed  diet,  gives  from  22  to 
35  grammes,  and  Beale  from  25  to  40  grammes.  Mehu  gives 
the  low  average  of  from  15  to  20  grammes. 

Chemistry.  Artificial  Production  of  Urea.— To  Wohler 
(1828)  is  due  the  credit  of  having  first  artificially  produced  urea. 
To  accomplish  this,  ammonium  sulphate  and  potassium  cyanate 
are  dissolved  in  water  in  equivalent  proportions,  and  the  solution 
evaporated  to  dryness.  The  following  reaction  takes  place  : 
(NH4)2S04+2KCNO=2NH4NCO  +  K2S04. 

*  Soc.  de  Biolog.,  1870,  pp.  75,  110,  and  Gaz.  Heb.  de  Med.  et  de 
Chir.,  1870. 


NORMAL  ELEMENTS  OF  THE   URINE.  47 

On  boiling  the  solution  of  ammonium  cyanate  a  molecular  change 
ensues,  the  latter  becoming  converted  into  isomeric  urea,  thus  : 

NH4NCO=(NH2)2CO. 
Potassium  cyanate  is  easily  made  by  the  oxidation  of  potassium 
cyanide,  and  potassium  cyanide  is  obtained  by  heating  potassium 
ferrocyanide.  Thus  we  have  the  preparation  of  urea  on  a  large 
scale.  Take  28  parts  of  K4Fe(CN)6  and  14  parts  of  peroxide 
of  manganese  (Mn02),  previously  well  mixed  and  dried,  and 
subject  the  mixture  to  slow  combustion.  Cyanate  of  potassium 
is  thus  obtained.  The  mass  is  treated  with  cold  water,  and 
subsequently  decomposed  by  the  addition  of  20^  parts  of  sul- 
phate of  ammonia.  The  resulting  compound  is  evaporated  to 
dryness  in  a  water-bath.  Urea,  sulphate  of  potash,  and  an 
excess  of  ammonium  sulphate  remain.  Absolute  alcohol  is 
then  added,  which  dissolves  out  the  urea,  leaving  the  other 
constituents  untouched.  By  filtering  and  evaporation  the  urea 
is  deposited  in  beautiful  crystals  of  considerable  size.  This  is 
the  best  method  of  preparing  urea  ;  but  it  may  also  be  prepared 
by  the  action  of  oxychloride  of  carbon  (phosgene  gas)  on  ammonia, 

(COCl2+2NH3=CO(NH2)2+2HCl)  ; 
of  ethyl  carbonate  on  ammonia, 

(C03(C2H5)2+2NH3=CO(NH2)2-f2C2H60), 
and  of  mercuric  oxide  on  oxamide 

C202(NH2)2+HgO=CO(NH2)2+C02+Hg). 

M.  Bechampt  has  succeeded  in  producing  urea  by  the  oxida- 
tion with  permanganate  of  potash  of  certain  nitrogenous  sub- 
stances, such  as  gluten,  and  these  observations  are  confirmed 
by  Kitter.  Urea  is  also  produced  by  the  action  of  peroxide  of 
lead  upon  uric  acid,  and  also  by  the  action  of  alkalies  upon 
alloxan  and  creatine. 

Physical  Properties. — From  an  aqueous  solution  urea  crys- 
tallizes in  the  form  of  quadratic  prisms  with  a  rectangular 
terminal  plane.  From  an  alcoholic  solution  the  planes  are 
octahedral.  It  is  of  colourless  appearance,  and  possesses  a 
fresh  odour  like  that  of  nitre.  It  is  soluble  in  an  equal  weight 
of  cold  water,  and  in  a  much  smaller  quantity  at  a  high  tem- 
perature.   It  is  easily  soluble  in  alcohol,  sparingly  soluble  in 


48 


THE  URINE  IN  HEALTH  AND  DISEASE. 


ether,  and  quite  insoluble  in  oil  of  turpentine.  The  crystals 
polarize  with  a  faintish-blue  colour.  It  possesses  a  somewhat 
bitter  saline  .taste. 

Urea  constitutes  a  base  which  gives  with  most  diluted  acids 
well-defined  crystalline  salts.    The  principal  salts  of  urea  are : 


Fig.  8.— Crystals  of  Urea. 


First,  the  Nitrate. — When  nitric  acid  is  added  to  a  sufficiently 
concentrated  solution  of  urea,  it  forms  a  crystalline  precipitate 
of  nitrate  of  urea — CO(NH2)2.  HN03.  The  precipitate  presents 
on  microscopic  examination  a  characteristic  appearance.  The 
crystals  consist  of  large,  yellow,  hexagonal,  and  sometimes 
rhomboidal  laminae,  overlapping  one  another  at  the  angles. 
If  this  salt  be  heated,  it  decomposes  towards  a  temperature  of 
140°,  giving  off  carbonic  acid  and  protoxide  of  nitrogen.  It  is 
less  soluble  in  water  than  urea,  and  is  very  little  soluble  in 
water  impregnated  with  alcohol  or  nitric  acid. 

Second,  Oxalate  of  Urea. — Oxalic  acid  added  to  a  solution 
of  urea  acts  similarly  to  nitric  acid,  and  forms  a  precipitate  of 
oxalate  of  urea — (CON2H4)2.  H2C204.  This  salt  crystallizes  in 
prismatic  scales.  It  is  soluble  in  water,  but  less  soluble  than 
the  nitrate.  It  can  be  dried  up  to  a  heat  of  100°,  but  at  150° 
it  decomposes.  Oxalic  acid  has  a  greater  affinity  for  urea  than 
nitric  acid  has,  so  that  when  added  to  a  solution  of  nitrate  of  urea 
a  precipitate  results  which  is  not  very  soluble  in  water  contain- 


NORMAL  ELEMENTS  OF  THE  URINE. 


49 


ing  nitric  acid.  If  chlorine  gas  is  passed  over  fused  urea, 
hydrochloric  acid  and  nitrogen  are  evolved,  and  there  remains 
a  mixture  of  sal  ammoniac  and  cyanuric  acid : 

6CO  (NH2)2 + 3C12  =  2C3H3N303  +  4NH4C1+2HC1 + N2. 
But  if  a  solution  of  urea  be  acted  upon  by  a  solution  of  chlorine 
gas  or  hypochlorous  acid,  the  decomposition  is  totally  different ; 
thus : 

CO(NHa)a+3ClHO  =  3HCl+C02+2H20+N2. 
Hydrochloric  acid,  carbon  dioxide,  water,  and  nitrogen  are 
thus  formed.  If,  instead  of  free  chlorine,  an  alkaline  hypo- 
chlorite be  used,  the  reaction  lis  the  same,  only  an  alkaline 
chloride  is  formed,  and  the  carbonic  acid  gas  is  not  disengaged, 
but  is  retained  by  an  excess  of  alkali.  The  more  alkaline  the 
medium,  the  more  complete  the  reaction  ;  thus  : 

CO(NH2)2+3NaC10  =  3NaCl+2H20  +  C0.2+N2. 
The  carbonic  acid  gas  is  retained  in  the  form  of  carbonate  of 
soda,  and  only  nitrogen  is  given  off. 


Fig.  9. — Crystals  of  Nitrate  of  Urea. 
Bromine  and  the  alkaline  hypobromites  act  in  a  similar 
manner,  but  more  energetically.  When  a  solution  of  urea  is 
mixed  with  an  excess  of  hypobromite  of  sodium,  the  former 
is  rapidly  decomposed,  and  evolves  about  90  per  cent,  of  its 
nitrogen : 

CO(NH2)2+3NaBrO  f  2NaOH  =  3NaBr+Na2C03  +  3H20+N2. 

4 


50 


THE  URINE  IN  HEALTH  AND  DISEASE. 


Heated  with  a  solution  of  nitrate  of  silver,  urea  gives  nitrate 
of  ammonia  and  an  insoluble  cyanate  of  silver. 

From  the  clinical  aspect,  it  may  be  observed  that  with  the 
addition  of  water  urea  is  transformed  into  carbonate  of  ammonia. 
This  reaction  is  facilitated  by  heat,  but  in  course  of  time  it 
takes  place  at  the  temperature  of  the  air  or  of  the  body : 

CO(NH2)2+2H20  =  (NH4)2C03. 

Nitrous  acid  or  nitric  acid  charged  with  nitrous  vapour  very 
rapidly  decomposes  urea.  This  reaction  has  been  interpreted  in 
various  manners,  but  according  to  the  excellent  observations  of 
Bojmiond,  the  urea  is  decomposed,  giving  off  equal  volumes  of 
carbonic  acid  and  nitrogen  ;  thus  with  nitrous  acid  : 

CO(NHa)2+2HNOa  =  C02+2N2+3H20. 

On  mixing  a  solution  of  urea  with  mercuric  nitrate,  a  white 
precipitate  consisting  of  CO(NH2)2,  2HgO  is  obtained  and  nitric 
acid  is  set  free.  If  the  nitric  acid  be  neutralized  by  the  addi- 
tion of  an  alkali  or  baryta  water,  the  whole  of  the  urea  may  be 
thus  removed.  It  is  on  this  reaction  that  Liebig's  process  for 
the  estimation  of  urea  is  based.  Phosphoric  acid  combines  with 
urea  to  form  a  soluble  phosphate.  This  salt  has  been  described 
and  studied  by  Lehmann,  who  found  it  in  the  urine  of  the  pig. 
Sulphuric  acid  does  not  combine  with  urea  ;  neither  does  uric, 
hippuric,  nor  lactic  acid. 

Extraction  and  Preparation  of  Urea.  —  Urea  may  be 
extracted  from  the  urine  by  various  processes.  The  simplest  is 
the  method  employed  by  Fourcroy  and  Vauquelin.  This  consists 
in  evaporating  the  urine  to  a  syrupy  consistence,  and  in  treating 
the  residue  with  absolute  alcohol.  Urea  as  thus  obtained  is  not, 
however,  in  a  very  pure  form,  and  is  difficult  of  crystallization. 
This  process  may  be  advantageously  modified  as  follows :  The 
alcoholic  solution  is  evaporated,  and  the  residue  dissolved  in  water, 
filtered,  and  precipitated  by  nitric  acid.  The  nitrate  of  urea  thus 
obtaine  1  is  collected,  washed  with  water,  and  then  decomposed  by 
boiling  with  a  solution  of  either  bicarbonate  of  potash,  carbonate 
of  baryta,  or  carbonate  of  lead.  The  mixture  is  then  evaporated 
and  treated  with  concentrated  alcohol,  which  dissolves  the  urea 
alone.     This  process  has  the  following  disadvantages :  The 


NOKMAL  ELEMENTS  OF  THE  URINE. 


51 


nitrate  of  urea  is  not  entirely  insoluble  in  water,  and  con- 
sequently there  is  always  loss.  Further,  a  certain  proportion  of 
nitro-muriatic  acid  is  formed  with  the  chlorides  of  the  urine.  A 
better  method  consists  in  precipitating  the  sulphates  and  phos- 
phates of  the  urine  by  the  addition  of  half  its  volume  of  a  solu- 
tion of  baryta,  filtering,  and  evaporating  to  dryness  on  a  sand- 
bath.  The  residue  is  dissolved  by  absolute  alcohol  and  evaporated. 
Two  crystallizations  may  be  requisite.  The  urine  of  the  dog  is 
much  richer  in  urea  than  that  of  man,  and  may  thus  be  more 
conveniently  employed  for  purposes  of  investigation  and  experi- 
ment relating  to  urea. 

Quantitative  Analysis  of  Urea.— For  few  substances  have 
more  processes  of  volumetric  analysis  been  employed  than  for 
urea.    The  following  are  the  simplest  and  most  reliable  : 

First,  the  process  of  decomposition  by  the  hypochlorites 
(Leconte). 

Second,  the  process  of  decomposition  by  means  of  nitric  acid, 
on  which  are  based  the  methods  of  Millon  and  Liebig. 

Third,  the  process  of  decomposition  by  alkaline  hypobromites. 
Process  of  Ldconte.—  We  have  already  seen  (vide  p.  49) 


Fig.  10. 

A,  Decomposing  flask  ;  B,  Graduated  tube  for  reception  of  nitrogen, 
that  urea  is  decomposed  by  chlorine  into  water,  carbonic  acid 
gas  and  nitrogen.    This  decomposition  is  similarly  effected  by 


52 


THE  URINE  IN  HEALTH  AND  DISEASE. 


the  hypochlorites,  e.g. — the  hypochlorite  of  soda.  To  prepare 
a  solution  for  this  purpose,  dissolve  100  grammes  of  well- 
powdered  '  chloride  of  lime  '  in  distilled  or  recently  boiled  and  cold 
water  ;  then  dissolve  in  the  filtered  fluid  200  grammes  of  crystal- 
lized carbonate  of  soda  reduced  to  powder  ;  wash  the  resulting 
carbonate  of  lime,  and  make  up  to  2  litres.  This  solution  should 
be  preserved  in  a  stoppered  bottle. 

The  figure  on  page  51  represents  the  apparatus  of  Leconte. 

Proceed  as  follows  :  Take  from  10  to  20  grammes  of  the  urine, 
which  introduce  into  a  flask  of  a  capacity  of  from  120  to  200 
cubic  centimetres.  Fill  the  flask  with  the  hypochlorite  solution, 
and  close  the  orifice  by  means  of  a  cork  through  which  a  glass 
tube  communicates  with  a  graduated  receiver  full  of  water. 
Decomposition  at  once  ensues,  especially  at  the  summer  tempera- 
ture. It  is  desirable,  however,  to  apply  heat  by  means  of  a 
spirit-lamp.  The  mixture  is  raised  to  the  temperature  of  ebulli- 
tion, and  thus  maintained  until  no  more  gas  is  evolved.  The 
carbonic  acid  is  retained  in  the  flask,  and  nitrogen  alone  is  col- 
lected in  the  receiver.  On  examining  the  formula  of  urea  it  will 
be  found  that  theoretically  10  centigrammes  (0*10)  correspond  to 
37  cubic  centimetres*  of  nitrogen,  measured  at  a  temperature  of 
0°  and  the  normal  pressure  of  760  millimetres;  but  Leconte  has 
not  been  able  to  obtain  more  than  34  cubic  centimetres  by  means 
of  the  hypochlorite  of  soda,  and  this  figure  (34)  is  adopted  gener- 
ally as  the  basis  of  calculation,  though  some  other  authorities 
maintain  that  the  nitrogen  given  off*  is  short  of  the  absolute 
amount  by  6  cubic  centimetres. 

If  34  c.c.  of  nitrogen  be,  then,  equivalent  to  10  centigrammes 
(0*10)  of  urea,  a  simple  proportion  sum  will  give  the  urea 
corresponding  to  the  volume  of  nitrogen  collected  in  the 
receiver.    In  order  to  obviate  errors  which  may  arise  in  the 

*  That  one  decigramme  of  urea  will  yield  at  a  temperature  of  0°  and 
a  pressure  of  760  mill.  37  c.c.  of  nitrogen  is  evident  from  the  following  : 
1  litre  of  nitrogen  at  0°  760  m.m.  =  1*2562  grms.  Combining  weight 
of  urea  =  60.  Then,  if  60  give  28  N  by  weight,  what  will  0'1  of  urea 
give?  (60  :  0*1  ::  28  :  #  =  0*046) — and,  of  course,  1  grm.  of  urea  gives 
0*46,  or  ten  times  as  much  as  the  decigramme.  Now,  1  litre  of  nitrogen 
(1,000  c.c.)  at  0°  760  m.m.  =1*2562  grins.  ;  hence  1*2562 grms.  :  0*46  grm. 
::  1,000  :  x  =  371*48  c.c.  nitrogen,  and  a  decigramme  37*1  c.c. 


NOKMAL  ELEMENTS  OF  THE  UEINE. 


53 


course  of  this  experiment  from  the  presence  of  albumen  and  uric 
acid  which  may  be  partially  decomposed  by  the  chlorine,  and 
thus  evolve  nitrogen,  the  urine  ought  previously  to  be  purified  as 
follows :  To  20  grammes  of  urine,  3  grammes  of  subacetate  of 
lead  are  added.  The  fluid  is  boiled,  filtered,  and  the  residue 
well  washed ;  then  3  grammes  of  crystallized  carbonate  of  soda 
are  added.  This  fluid  is  in  turn  boiled,  filtered  and  the  residue 
washed.  As  the  volume  of  the  fluid  has  been  augmented  by  the 
washings,  the  half,  which  represents  10  grammes  of  urine,  is 
sufficient  for  the  purpose  of  experiment. 

Process  of  Millon. — This  process  is  based  on  the  decomposi- 
tion of  urea  by  a  solution  of  nitrate  of  mercury  charged  with 
nitrous  vapour.    Thus  : 

2CO  (NH2)2+N203+2HN03  =  2C02+2N2+H30+2NH4N03. 

The  nitric  acid  is  here  employed  in  the  form  of  a  nitrate  and 
nitrite  of  mercury,  with  an  excess  of  nitric  acid. 

The  reagent  is  prepared  by  dissolving  125  grammes  of  mercury 
in  168  grammes  of  nitric  acid  of  a  density  of  1*44,  and  then 
diluting  with  twice  the  volume  of  water.  Equal  volumes  of 
carbonic  acid  gas  and  nitrogen  are  given  off.  It  is  with  the 
former  alone  that  the  process  of  Millon  deals,  and  its  amount 
is  thus  estimated  :  This  gas  is  received  in  a  tube  containing  a 
portion  of  caustic  potash.  Prior  to  the  commencement  of  the 
experiment  this  tube  is  carefully  weighed  in  a  chemical  balance. 
Subsequently  the  two  gases  pass  over  the  caustic  potash,  but  the 
carbonic  acid  gas  alone  is  absorbed,  and  its  weight  is  represented 
by  the  additional  weight  of  the  tube.  This  increased  weight 
multiplied  by  1*3636*  gives  the  weight  of  urea  contained  in  the 
specimen  of  urine  operated  on.  Twenty  grammes  of  urine 
should  be  introduced  into  a  flask  having  a  capacity  of  200  cubic 
centimetres,  and  50  cubic  centimetres  of  the  reagent  of  Millon 
should  be  employed. 

Process  of  Liebig. — This  process  consists  in  the  successive 
employment  of  a  solution  of  baryta,  which  separates  the  sul- 
phates and  phosphates  of  the  urine ;  a  solution  of  nitrate  of 

*  Combining  weight  of  urea,  60  ;  carbonic  acid  44  .*.  60  -f  44  =  1*3636  ; 
hence  C02  x  T3636  =  urea  in  the  *20  grammes  of  urine  submitted  to 
analysis.  ■ 


54 


THE  URINE  IN  HEALTH  AND  DISEASE. 


mercury,  which  decomposes  the  urea  ;  and  a  solution  of  carbonate 
of  soda,  which  indicates  when  the  reaction  is  complete.  The 
solution  of  nitrate  of  mercury  is  so  prepared  that  1  cubic  centi- 
metre of  it  corresponds  to  1  centigramme  (0*01)  of  urea.  The 
mercuric  nitrate  decomposes  the  chlorides  into  sodic  nitrate, 
potassic  nitrate  and  mercuric  chloride,  and  then  combines  with 
urea  as  under. 

The  precipitate  varies  in  composition,  according  to  the  degree 
of  concentration  of  the  fluid.  The  composition  is  represented  by 
one  of  the  three  following  formulae  : 

HN03Ur-f2HgO 

HN03Ur+3HgO 

HN03  +  Ur+4HgO 
In  a  solution  of  chloride  of  sodium  containing  urea,  a  per- 
manent precipitate  of  urea  and  oxide  of  mercury  is  not  formed 
by  a  solution  of  the  nitrate  of  mercury  until  the  whole  of  the 
chloride  of  sodium  present  has  been  decomposed  and  the  nitrate 
thus  converted  into  corrosive  sublimate.  Immediately  on  the 
chloride  of  sodium  being  thus  decomposed,  the  next  drop  of  the 
solution  of  mercury  throws  down  a  permanent  deposit  of  oxide 
of  mercury  and  urea,  which  is  insoluble  in  water. 

Preparation  of  Liebigs  Standard  Solution.— Dissolve  in 
strong  nitric  acid  by  aid  of  heat  77*2  grammes  (1,196*6  grains)  of 
dry  oxide  of  mercury,  so  pure  that  on  being  heated  on  a  platinum 
spatula  no  residue  is  left.  Evaporate  the  solution  to  the  con- 
sistence of  a  syrup,  and  then  dilute  up  to  1,000  c.c.  with  distilled 
water.  If  any  precipitate  of  basic  salt  form,  add  a  few  more 
drops  of  nitric  acid.  One  c.c.  of  this  solution  is  equal  to  0*01 
gramme  (0*15  grain)  of  urea. 

Baryta  Solution. — Mix  1  part  of  cold  saturated  solution  of 
nitrate  of  baryta  with  2  parts  of  a  cold  saturated  solution  of 
caustic  baryta,  and  reduce  the  mixture  to  half  its  strength  by 
addition  of  an  equal  amount  of  distilled  water. 

Carbonate  of  Soda  Solution. — A  saturated  solution,  or  about 
1  gramme  to  30  grammes  of  water,  or  20  grains  in  1  ounce  of 
water.  Dr.  Harley  has  suggested  for  convenience  the  impreg- 
nating of  white  filter  paper  with  the  soda  solution.  The  paper 
may  be  cut  into  strips  of  convenient  size,  and  preserved  in 


NORMAL  ELEMENTS  OF  THE  URINE. 


55 


a  wide -mouthed  stoppered  bottle.  A  drop  of  the  mixture  to 
which  a  sufficient  quantity  of  the  nitrate  of  mercury  has  been 
added  will  stain  this  paper  yellow  (oxide  of  mercury). 

Volumetric  Analysis. — With  a  graduated  pipette,  take,  for 
example,  40  c.c.  of  the  urine  to  be  examined,  to  which  add  20  c.c. 
of  the  baryta  solution.  Stir  the  resulting  mixture,  and  filter.  Of 
this  liquid  take  15  c.c,  which  obviously  correspond  to  10  c.c.  of 
urine,  and  add  a  few  drops  of  nitric  acid.  Place  these  15  c.c.  of 
the  mixture  in  a  glass  flask  or  glass  beaker,  and  to  this  quantity 
add  drop  by  drop  the  nitrate  of  mercury  solution.  The  first  drops 
produce  no  precipitate,  as  they  form  with  the  chlorides  of  the 
urine  a  soluble  bichloride  of  mercury.  The  chlorides  having 
thus  entered  into  a  new  combination,  the  next  addition  of  the 
nitrate  of  mercury  solution  causes  a  permanent  precipitate  of 
urea  and  oxide  of  mercury  (1  equivalent  of  the  former  to 
2  equivalents  of  the  latter,  or  more,  according  to  concentration). 
The  quantity  of  the  nitrate  of  mercury  solution  necessary  for 
the  saturation  of  the  chlorides  is  carefully  noted,  and  sub- 
tracted from  the  total  required  to  be  added  until  a  drop  of 
the  solution  gives  a  yellow  colour  in  contact  with  a  drop  of  the 
solution  of  the  carbonate  of  soda.  The  yellow  colour  does  not 
appear  with  the  carbonate  of  soda  solution  until  1  volume 
of  the  solution  of  mercury,  containing  77  parts  of  the  oxide 
has  been  added  to  every  10  parts  of  urea — that  is,  4  equivalents 
of  the  mercury  to  1  of  urea.* 

If  a  bluish  colour  result  with  the  soda  solution,  it  is  indicated 
that  there  is  still  free  urea  in  the  solution ;  a  yellow  colour 
(HgO — '  yellow  wash  '),  that  there  is  no  free  urea,  but  that  there 
is  an  excess  of  the  nitrate  of  mercury.  Every  cubic  centimetre 
or  every  fractional  part  of  the  mercurial  solution  required  for  the 
second  part  of  the  experiment  corresponds  to  a  centigramme 
(0*01),  or  a  corresponding  fractional  part  of  urea.  The  amount 
of  urea  in  10  c.c.  being  thus  ascertained,  it  is  a  question  of  simple 
proportion  to  determine  the  daily  excretion  of  urea.  Thus,  sup- 
posing that  1  c.c.  of  the  solution  was  required  to  saturate  the 

*  Theoretically,  100  parts  of  urea  should  require  720  parts  of 
mercuric  oxide,  but  the  solution  must  be  in  excess  to  give  the  yellow 
colour. 


56 


THE  URINE  IN  HEALTH  AND  DISEASE. 


chlorides,  and  that  altogether  19  c.c.  were  used  before  the  yellow 
coloration  with  the  carbonate  of  soda  solution  was  distinctly 
produced,  then  :  19  —1  =  18  =  18  centigrammes  of  urea  (0*18).  If 
the  patient  passed  in24hou«rs  1,850  c.c.  of  urine,  then  10  :  1,850 
::  18  :  #  =  3,330  centigrammes,  or  divided  by  100  =  33*30  grammes. 

By  another  process  the  chlorides  may  be  separated  from  the 
urine  by  a  standard  solution  of  nitrate  of  silver,  of  which  1  c.c. 
corresponds  to  a  centigramme  of  chloride  of  sodium.  To  prepare 
this  solution,  take  of 

Pure  recrystallized  nitrate  of  silver,  29*075  grammes : 
Distilled  water  to  1,000  c.c. 

Let  10  c.c.  be  taken,  and  the  amount  of  chloride  of  sodium  be 
determined  by  the  silver  solution,  as  by  the  method  for  determi- 
nation of  chlorides  (vide  infra).  If  it  is  found  that  15  c.c. 
ara  required  for  this  purpose,  0*15  centigrammes  of  sodium 
chloride  are  indicated.  Then  take  30  c.c.  (containing  20  c.c.  of 
urine)  of  the  filtrate  from  the  mixture  of  baryta  fluid  and  urine, 
add  a  drop  or  two  of  nitric  acid.  Then  if  10  require  15  of  the 
silver  solution,  20  must  require  30.  This  should  precipitate  all 
the  chlorides,  which  can  now  be  removed  by  filtration. 

Additional  Corrections. — The  mercury  solution  is  graduated 
for  a  solution  of  urea  which  contains  2  per  cent,  of  urea  ;  hence 
30  c.c.  of  the  mercury  solution  are  required  for  the  complete 
precipitation  of  the  urea  in  15  c.c.  of  the  urea  solution.  The 
mixture  thus  amounts  to  45  c.c,  in  which  there  are  30  times  5*2 
=  156  milligrammes  of  free  oxide  of  mercury  ;  every  c.c,  there- 
fore, contains  3*47  milligrammes  of  oxide  of  mercury.  If  the  15 
c.c  of  urea  solution  contain  4  per  cent,  of  urea,  and  we  add  60 
of  the  mercurial  solution,  a  mixture  amounting  to  75  c.c.  is  pro- 
duced, in  which  there  are  312  milligrammes  of  the  oxide  of 
mercury  (60x5*2),  or  4*16  milligrammes  in  every  c.c,  being, 
therefore,  an  excess  of  0*69  milligrammes  (4*16— 3*47)  of  oxide 
in  every  cubic  centimetre  above  what  is  required  to  produce  the 
final  reaction  with  carbonate  of  soda.  It  is,  therefore,  clear  that 
in  experimenting  on  urine  containing  a  larger  amount  of  urea 
than  2  per  cent.,  the  urea  will  appear  smaller  than  it  really  is. 
If  the  urine,  as  in  the  example  given,  contain  4  per  cent.,  we 
should  not  add  60  c.c,  but  only  59*37  c.c.  of  the  mercury  solution. 


NOEMAL  ELEMENTS  OF  THE  UKINE. 


57 


To  avoid  this  error,  as  soon  as  it  is  found  that  the  percentage 
of  urea  is  higher  than  that  for  which  the  mercurial  solution  is 
graduated,  add  for  every  additional  c.c.  of  this  solution  required  a 
half  of  water  before  testing  with  the  carbonate  of  soda.  If,  for  ex- 
ample, we  have  used  20  c.c.  more  than  30,  we  add  10  c.c.  of  water. 

Modification  when  the  Urea  sinks  below  1  per  cent.— 
Should  the  quantity  of  the  urea  in  the  urine  amount  to  only 
1  per  cent.,  we  must  add  to  15  c.c.  of  urine,  not  15  c.c.  of  the 
mercury  solution,  but  15*3  before  the  final  test-point  is  reached. 
In  consequence  of  this  source  of  error,  the  amount  of  urea 
obtained  is  too  great.  In  operating,  then,  on  dilute  urine,  for 
every  5  c.c.  of  the  mercury  solution  less  than  30  which  has  been 
used,  subtract  0*1  c.c.  from  the  total  amount  employed.  If,  thus, 
for  15  c.c.  of  urine  25*0  c.c.  of  mercurial  solution  have  been 
used,  the  real  amount  of  urea,  being  249  milligrammes,  is  ex- 
pressed by  24*9  c.c.  of  mercurial  solution. 

The  Urine  contains  Albumen. — In  this  case  50  c.c.  of  the 
urine  are  treated  with  2  drops  of  strong  acetic  acid,  and  boiled  to 
coagulate  the  albumen ;  the  precipitate  is  allowed  to  settle,  and 
30  c.c.  of  the  clear  urine  are  mixed  with  15  c.c.  of  the  baryta 
solution,  filtered,  and  treated  as  already  described. 

Liebig's  process  is  thus  a  troublesome  one,  subject  to  errors 
requiring  correction,  and  for  simplicity  and  accuracy  is  of  inferior 
value  to  one  or  other  of  the  methods  of  determining  the  amount 
of  urea  by  the  alkaline  hypobromites. 

Volumetric  Analysis  of  Urea  by  Hypobromite  Process. — 
This  process  is  based  upon  the  fact  that  hypobromous  acid 
decomposes  urea  into  carbonic  acid,  water  and  nitrogen.  The 
decomposition  is  as  follows  : 

CO(NH2)2+ 3NaBrO  -  3NaBr  +  C02  -r-2H20  +N2. 
In  this  process  the  volume  of  nitrogen  disengaged  is  the  measure 
of  urea. 

The  hypobromite  solution  is  best  prepared  by  dissolving 
100  grammes  (3 J  ounces)  of  common  caustic  soda  in  250  c.c. 
(9  ounces)  of  water,  and  when  cold*  adding  25  c.c.  (7  drachms) 
of  bromine. 

*  This  is  a  necessary  precaution,  for  unless  the  bromine  be  added  to 
the  soda  solution  when  perfectly  cold,  the  proper  amount  of  nitrogen  is 
not  evolved  when  the  experiment  is  conducted. 


58 


THE  URINE  IN  HEALTH  AND  DISEASE. 


We  have  already  seen  (vide  footnote,  p.  52)  that  1  gramme 
of  urea  yields  0*46  gramme  of  nitrogen  by  weight,  and  occupies 
a  volume  of  371*48  c.c.*  at  0°  and  760  m.m.  It  therefore 
follows  that  every  cubic  centimetre  of  nitrogen  evolved,  after  a 
given  quantity  of  urine  is  treated  with  the  hypobromite  solution, 
represents  a  corresponding  fractional  part  of  a 
gramme  of  urea.  Supposing  the  tube  for  the  recep- 
tion of  the  nitrogen  to  be  graduated  into  cubic  centi- 
metres, and  that  37 '1  c.c.  of  nitrogen  are  evolved, 
it  follows  that  this  represents  the  tenth  part  of  a 
gramme  or  Ol  of  urea.  In  this  calculation  the 
normal  temperature  and  pressure  are  assumed. 
While  37*1  c.c.  is  absolutely  the  correct  number, 
Leconte  has  never  been  able  to  obtain  more  than 
{  «  34  c.c.  of  nitrogen  from  a  decigramme  of  urea,  and 
g  consequently  34  is  usually  adopted,  especially  in 
o  France,  as  the  basis  of  calculation,  and  as  being 
equivalent  to  Ol  of  urea  at  0°  and  760  m.m.  There- 
in fore,  supposing  25  c.c.  of  nitrogen  have  been  evolved 
§  f  rom  the  urine  experimented  upon  : 
|x  34  c.c.  :  25  ::  0*1  :  #  =  *073  gramme  of  urea. 
[  It  will  be  obvious  that,  to  ascertain  the  quantity 
rH  of  urea  passed  in  twenty-four  hours,  it  will  be 
2  necessary  to  know  the  volume  of  urine  passed  in 
^  twenty-four  hours,  and  of  the  urine  operated  upon. 
With  a  view  to  obviate  the  necessary  corrections 
for  temperature  and  pressure,  Yvon  has  suggested 
the  employment  of  this  instrument.  It  consists  of 
a  glass  tube  of  40  centimetres  in  length.  Towards 
its  upper  extremity  it  is  traversed  by  a  stop-cock, 
on  either  side  of  which  the  tube  is  graduated 
into  tenths  of  a  c.c.  The  instrument  is  inserted 
into  a  long  narrow  tube  containing  mercury,  the 
stop-cock  is  opened,  and  the  lower  portion  of  it  is 
thus  filled  with  the  mercury.  The  stop-cock  is  then  closed  and 
the  instrument  raised,  and  supported  in  the  tube  by  means  of 


*  371-48  c.c.  N2  :  1  c.c.  N2  ::  1  gr.  :  x  =  '002689  gr.  urea. 


NORMAL  ELEMENTS  OF  THE  URINE. 


59 


Fig.  12.  —  Gerrard's 
Ureometer.*  —  This  in- 
strument consists  of  two 
tubes  of  unequal  diameter 
and  length,  and  connected 
by  a  piece  of  indiarubber 
tubing.  The  longer  tube 
is  filled  from  the  shorter 
with  water,  and  is  gradu- 
ated for  the  estimation  of 
the  nitrogen  received  from 
a  bottle  also  connected  with 
it  by  indiarubber  tubing, 
and  in  which  the  decom- 
position of  the  urine  takes 
place  by  means  of  the  hypo- 
bromite  solution.  The  top 
of  the  measuring- tube  is 
connected  with  a  tube  of 
indiarubber,  which  may 
be  closed  by  a  clamp. 

Method  of  Using. — Pour 
into  a  test-tube  5  c.c.  of 
the  urine  to  be  examined, 
and  in  the  bottle  (a)  25  c.c, 
or  six  fluid  drachms,  of 
sodium  hypobromite  solu- 
tion. Place  the  tube  carefully  inside  the  bottle,  as  shown  on  the 
illustration,  taking  care  to  avoid  any  spilling  of  the  contents.  Pill 
the  glass  tube  (b  c)  with  water,  so  that  the  level  reaches  the  zero  line, 
taking  care  that  when  this  is  done  the  tube  (c)  contains  only  a  little 
water  by  being  placed  high — it  having  to  receive  what  is  displaced 
from  (c)  by  the  nitrogen  evolved.  The  clamp  at  the  top  of  the  long 
tube  having  been  open  to  relieve  pressure,  this  is  now  shut.  Then 
connect  the  indiarubber  tubing  to  the  bottle,  note  that  the  water  is 
exactly  at  zero,  and  upset  the  contents  of  the  test-tube  into  the  hypo- 
bromite solution.  Nitrogen  is  evolved,  which  depresses  the  water  in 
(b).  When  this  ceases,  lower  the  tube  (c)  until  the  level  of  the  water 
in  both  tubes  is  equal.  The  tube  is  graduated  in  per  cents,  of  urea, 
and  cooling  for  five  or  ten  minutes  should  be  allowed  to  take  place 
before  the  readings  are  taken.  The  solution  of  hypobromite  of  soda 
is  made  by  dissolving  100  grammes  of  caustic  soda  in  250  c.c.  of  water, 
and  when  cold  22  c.c.  of  bromine  are  added.  To  obviate  the  disagree- 
able smell  and  dangers  of  the  bromine  vapour,  the  bromine  can  be 
obtained  in  hermetically-sealed  glass  tubes  containing  2  c.c.  One  of 
these,  placed  in  the  large  bottle  with  25  c.c.  of  the  soda  solution,  gives, 
when  broken  with  a  sharp  shake,  the  exact  quantity  of  hypobromite 
for  one  estimation  of  urea. 


*  Manufactured  by  Gibbs,  Cuxson  and  Co.,  Wednesbury. 


60 


THE   URINE  IN  HEALTH  AND  DISEASE. 


the  arm  of  an  ordinary  stand.  A  kind  of  mercurial  barometer 
is  thus  formed,  into  the  chamber  of  which  it  is  possible  to 
introduce  fluids  without  the  admixture  of  air. 

A  standard  solution  of  urea  is  first  prepared,  containing  1 
centigramme  (O01)  in  5  c.c,  and  this  is  measured  in  the  upper 

Tig.  13. — Ukeometer  of  Dobemus.* 
— This  simple  instrument,  originally 
designed  by  Dr.  Charles  Doremus,  of 
New  York,  gives  fairly  accurate  results. 

Directions  for  Use. — Fill  the  vertical 
tube  with  a  solution  of  hypobromite  of 
sodium,  by  pouring  the  solution  into 
the  bulb  until  it  is  about  half  full. 
The  apparatus  should  then  be  inclined 
horizontally  until  the  entire  tube  is 
filled,  about  one-third  being  left  in  the 
bulb.  Then  restore  the  apparatus  to 
the  vertical  position.  Draw  into  the 
pipette  1  c.c.  of  the  urine  to  be  tested, 
pass  the  pipette  into  the  apparatus, 
the  point  being  placed  immediately 
under  the  long  arm.  Compress  the 
indiarubber  cap  plowly,  and  the  gas 
which  is  liberated  will  thus  pass  up 
the  long  tube.  It  now  collects  in  the 
upper  part  of  the  tube,  and  its  volume 
being  read  off,  indicates  the  amount  of 
urea  from  which  it  has  been  evolved.  In  cases  where  there  is  much 
urea,  it  is  advisable  to  mix  the  urine  with  an  equal  amount  of  water 
before  testing.  In  this  case  the  result  will  be  equal  to  one-half  of 
that  indicated  on  the  scale.  Each  division  of  the  instrument  indicates 
•001  gramme  of  urea  in  1  c.c.  of  urine.  The  percentage  of  urea  is 
obtained  by  multiplying  the  result  of  the  test  by  100.  To  ascertain 
the  total  amount  of  urea  voided  in  twenty-four  hours,  multiply  the 
result  by  the  number  of  c.c.  of  urine  parsed  during  that  period.  The 
instrument  is  also  graduated  to  the  English  scale,  each  division  indi- 
cating one  grain  of  urea  per  fluid  ounce  of  urine. 

part  of  the  tube,  which  is  correspondingly  graduated.  Turning 
the  stop-cock,  the  fluid  descends  into  the  lower  portion  of  the 
tube,  and  the  mercury  descends  correspondingly.  The  tube  is 
then  washed  with  a  small  quantity  of  a  solution  of  caustic  soda, 
which  is  mixed  with  the  urea  solution.  Then  from  5  to  6  c.c.  of 
the  hypobromite  solution  are  introduced  into  the  upper  part  of 

*  Manufactured  by  Southall  Bros,  and  Barclay,  Birmingham. 


NORMAL  ELEMENTS  OF  THE  URINE. 


61 


the  tube,  communication  with  the  lower  part  being  meantime  shut 
off.  By  turning  the  stop-cock  admixture  of  the  fluids  takes  place, 
and  reaction  immediately  commences,  but  no  gas  escapes,  the 
pressure  being  more  feeble  inside  than  outside.  To  facilitate 
the  admixture  of  the  fluids,  the  thumb  is  placed  on  the  lower 
portion  of  the  tube  and  the  instrument  shaken.    It  is  now  re- 


Fig.  14. — Ureometer  of  Noel. 
Mode  of  Uaing. — Fill  the  gauge  E  with  water  to  within  one  or  two 
centimetres  below  the  zero  mark  of  the  graduated  jar  C.  Then  pour 
15  c.c.  of  hypobromite  solution  into  the  tube  H,  and  2  c.c.  of  urine  into 
the  small  graduated  tube  U,  and  about  2  c.c.  of  a  saccharine  solution. 
Establish  the  connections.  Note  that  the  level  of  the  water  in  C  is 
at  zero.  Incline  the  tube  H.  When  the  evolution  of  the  gas  has 
ceased  read  off  the  amount  of  nitrogen  in  the  graduated  tube  C. 

placed  in  the  receiving -tube  until  such  time  as  the  evolution  of 
all  the  nitrogen  has  taken  place.  The  fluid  then  becomes  of  a 
yellow  colour,  and  the  operation  is  terminated.  The  instrument 
is  now  introduced  into  a  tube  full  of  water,  when  the  more  dense 
hypobromite  solution  flows  out,  leaving  the  gas,  the  amount  of 
which  is  read  off.    This  operation  demonstrates  that  under 


62 


THE  URINE  IN  HEALTH  AND  DISEASE. 


the  conditions  in  which  the  experiment  is  conducted  a  given 
quantity  of  nitrogen  is  evolved.    Under  the  same  conditions  a 


Fig.  15.  — Noel's  Ureometer  Modified  by  Mehcier. 

In  this  apparatus  the  tube  E  is  filled  with  mercury  instead  of  water, 
so  that  any  error  from  solubility  of  the  nitrogen  in  the  water  is 
obviated.  C.  Tube  for  reception  of  the  nitrogen  divided  into  one- 
tenth  c.c.  ;  E,  Tube  containing  mercury  ;  T,  Empty  tube  ;  U,  gradu- 
ated urine-tube. 


NORMAL  ELEMENTS  OF  THE  UB1NE. 


63 


certain  quantity  of  urine  will  give  a  relative  amount  of  nitrogen 
gas.  This  comparison  obviates  the  troublesome  corrections  as  to 
temperature  and  pressure,  the  conditions  being  identical. 

Therefore,  if  1  centigramme  of  urea  register  40  divisions  of 
nitrogen  or  4  c.c,  and  if  a  c.c.  of  urine  give  88  divisions,  then 
40  :  88  ::  1 :  x  =  2  centig.  2  mill,  or  22  grammes  per  litre.  Another 
source  of  error  is  further  obviated  by  this  process,  viz.,  that 
arising  from  the  fact  that  the  hypobromite  does  not  separate 
more  than  about  92  per  cent,  of  the  nitrogen,  or  about  the  same 
relative  percentage  between  the  theoretically  correct  number, 
37  c.c,  which  a  decigramme  of  urea  ought  to  yield,  and  the 
34  which  practically  Leconte  found  it  to  yield. 

Yvon  used  another  ureometer,  in  which  water  takes  the  place 
of  mercury,  but  as  the  principle  is  the  same  the  process  need  not 
be  here  described. 

Should  the  urine  be  found  to  be  rich  in  urea,  it  may  be  diluted 
with  twice  or  four  times  its  volume  of  water,  and  the  result 
multiplied  accordingly. 

Hypobromite  of  soda  not  only  decomposes  urea,  but  it  like- 
wise decomposes  creatine,  creatinine,  uric  acid,  and  the  urates. 
In  very  exact  analysis  allowance  must  be  made  for  this. 

In  order  to  eliminate  the  error  in  connection  with  the  urates 
the  following  procedure  should  be  adopted  :  Take  10  c.c.  of 
urine,  to  which  add  1  c.c.  of  a  solution  of  subacetate  of  lead, 
then  sufficient  water  to  make  up  to  5  c.c,  and  filter.  The  urates 
are  separated  in  the  stats  of  urate  of  lead,  and  the  excess  of  lead 
in  the  solution  does  not  prevent  the  decomposition  of  urea  by  the 
hypobromite  of  soda.  The  oxide  of  lead  at  first  formed  is  dis- 
solved in  the  alkaline  fluid.  The  excess  of  subacetate  of  lead 
may  be  removed  by  carbonate  of  soda.  For  this  purpose  take 
10  c.c  of  urine  in  a  graduated  tube,  and  add  a  solution  of  car- 
bonate of  soda  to  make  up  to  50  c.c,  shake,  and  filter.  The 
urine  is  thus  obtained  free  from  lead. 

Speaking  generally,  an  augmentation  of  nitrogen  to  an  extent 
of  4*5  per  cent,  may  be  allowed  as  arising  from  other  sources 
than  urea,  and  for  clinical  purposes  it  will  be  sufficient  to 
subtract  4  per  cent,  from  the  amount  of  nitrogen  obtained. 
Hence,  if 


64 


THE  URINE  IN  HEALTH  AND  DISEASE. 


1  centigramme  of  urea  =  say,  39  divisions  of  N, 

1  cubic  centimetre  of  urine     =       68  ,, 

then 

39  :  68  ::  0*01  :  £=0'01743  and  per  litre  17'43  grammes, 

then 

100  :  17-43  ::  4-5  :  ^  =  0*78  and  17'43  gr.  -  0*78  =  16*65  gr., 
which  represents  very  nearly  the  quantity  of  urea  contained  in 
a  litre. 

M.  Mehu  has  made  the  very  interesting  and  important  ob- 
servation that  with  urine  containing  glucose  the  hypobromite 
separates  all  the  nitrogen  contained  in  the  urea.  Hence,  in 
conducting  a  volumetric  analysis  of  urea,  a  watery  solution  of 
glucose  may  be  used,  instead  of  distilled  water  for  diluting  the 
urine. 

Pathological  Significance. — Urea  represents  the  complete 
oxidation  of  the  nitrogenous  tissue  of  the  body,  and  probably 
to  some  extent  the  transformation  of  nitrogenous  constituents 
of  food.  It  will  follow  that  the  amount  of  urea  excreted  will 
be  in  a  direct  ratio  to  the  amount  of  tissue  disintegration,  and 
bear  consequently  a  relative  proportion  to  the  combustion  and 
temperature  of  the  body.  It  is,  therefore,  notably  increased 
in  all  febrile  affections,  in  inflammations  (such  as  pleurisy, 
pneumonia,  meningitis),  in  eruptive  fevers,  in  acute  articular 
rheumatism,  phthisis,  etc. 

In  typhus  fever  and  pneumonia  from  50  to  60,  or  even  80, 
grammes  (double  that  of  health)  may  be  excreted  during  the 
twenty-four  hours.  Increase  of  urea  in  febrile  affections  is  of 
graver  import  when  the  ingestion  of  nitrogenous  matter  is 
reduced  to  a  minimum.  As  the  fever  abates  its  excretion 
diminishes,  and  the  diminution  is  maintained  by  the  small 
amount  of  food  usually  taken,  or  the  impaired  functional 
activity  of  the  digestive  organs.  With  recurring  appetite  and 
strength  the  amount  of  urea  again  increases.  In  intermittent 
fever  the  urea  is  considerably  augmented  during  the  accession 
of  the  fever,  and  Ringer  and  Chalet  have  made  the  notable 
observation  that  the  urea  is  in  excess  before  the  thermometer 
indicates  an  elevation  of  temperature.  In  typhoid  fever  Parkes 
found  as  much  as  57  grammes  (883*5  grains)  in  the  urin  of 


NORMAL  ELEMENTS  OF  THE  URINE. 


65 


twenty-four  hours,  and  Vogel  in  one  case  the  large  amount  of 
78  grammes  (1,209  grains).  According  to  Sigmund,*  the  urea 
is  augmented  from  the  commencement  of  typhoid  fever.  In 
jaundice,  according  to  Bouchardat,  the  urea  is  considerably 
increased.  In  two  severe  cases  of  this  disease,  on  the  third 
and  fourth  day  he  found  from  59  to  133  grammes  of  urea  in 
twenty-four  hours'  urine.  In  a  case  of  chronic  cerebritis,  Dr. 
Harley  found  the  proportion  as  high  as  57*42  grammes  (890 
grains),  and  as  the  patient  recovered  it  fell  to  46*5  grammes 
(720*7  grains),  and  still  later  to  37*1  grammes  (574  grains), 
in  twenty-four  hours.  In  a  case  of  pyaemia,  Vogel  found 
80  grammes  (1,240  grains)  of  urea.  In  diabetes  the  amount 
is  greatly  increased.  Dr.  Harley  has  found  as  large  an  amount 
as  70  grammes  (1,085  grains)  in  the  twenty-four  hours'  urine  of 
a  gentleman  of  nearly  fifty  years  of  age.  The  same  authority 
states  that  the  average  of  twenty-nine  analyses  of  diabetic  urine 
yielded  47  grammes  (723*5  grains) — a  quantity  greatly  in  excess 
of  the  normal  amount.  To  some  extent  he  believed  this  to  be 
due  to  a  rich  animal  diet. 

In  certain  eruptive  fevers  the  amount  of  urea  is  likewise 
augmented.  Andral  found  in  a  case  of  urticaria  with  intense 
fever  30  per  1,000.  In  diabetes  the  amount  of  urea  excreted 
per  diem  is  augmented,  though  the  percentage  amount  is 
diminished  owing  to  the  large  quantity  of  urine  secreted. 
Durante  has  observed  a  similar  augmentation  in  varicella  and 
erysipelas  of  the  face. 

The  Amount  of  Urea  is  diminished,  conversely,  when  tissue 
metamorphosis  is  retarded,  and  there  is  deficient  oxidation  of 
tissue ;  thus,  in  anaemia,  with  deficient  red  corpuscles,  and 
consequently  deficient  oxidation,  pulmonary  emphysema,  heart 
affections,  cholera,  uraemia,  scorbutus,  Addison's  disease,  etc. 
Thudichum  states  that  the  lowest  amount  of  urea  he  has 
observed  to  be  discharged  by  a  patient  during  twenty-four  hours 
was  5  grammes  in  75  c.c.  of  pale,  faintly  alkaline  urine.  The 
patient  was  a  lady  suffering  from  anaemia,  and  an  abdominal 
tumour  caused  by  an  accumulation  of  faeces  which  had  escaped 
through  an  ulcerated  portion  of  the  intestine. 

*  Archiv.fiir  Physiol,  unci  Pathol.  Ch.  unci  Mic.  (Vienna,  1852) 

5 


66 


THE  URINE  IN  HEALTH  AND  DISEASE. 


According  to  Parkes,  uric  acid  can  always  be  found  in  the 
blood  after  all  nitrogenous  food  is  cut  off ;  and  this  is  held  by 
some  to  be  fatal  to  the  theory  of  deficient  oxidation  as  the  cause 
of  an  excess  of  uric  acid.  It  is  quite  possible  that  all  the  urea  is 
not  derived  from  the  uric  acid,  and  that  under  any  circumstances 


Fig.  16.— Ureometer  oe  Regnard. 

E  K,  Receiver  of  gas  ;  A,  Bulb  for  the  urine  ;  B,  Bulb  for  the 
reagent ;  /,  Glass  tube  to  diminish  pressure. 

Mode  of  Using. — Into  the  bulb  A  place  2  c.c.  of  the  urine  to  be 
examined  ;  into  B  about  10  c.c.  of  the  hypobromite  solution.  Estab- 
lish the  connections.  The  level  of  the  water  should  be  identical  in 
K  and  in  the  gauge  E.  This  is  accomplished  by  lowering  or  raising 
the  glass  tube  (I).  Incline  the  tube  so  that  the  two  liquids  may  come 
in  contact,  when  nitrogen  is  evolved  and  the  result  may  be  read  off. 

some  of  it  must  exist  in  the  blood,  and  that  thus  no  excess  of 
oxygen  would  cause  it  entirely  to  disappear.  Doubtless  the  other 
intermediate  products,  such  as  creatin  and  leucin  and  indican, 
contribute  to  the  formation  of  urea.  The  fundamental  prin- 
ciples of  physiology  point  to  oxidation  as  the  process  by  which  all 
the  ultimate  excreta  are  formed,  and  urea  can  be  no  exception. 


NORMAL  ELEMENTS  OF  THE  URINE. 


67 


In  Addison's  disease,  while  the  amount  of  urea  is  diminished, 
the  amount  of  indican  is  greatly  augmented.  Bosenstein,"*  in 
two  cases  of  this  nature,  found  that  the  urea  diminished  to  from 
20  to  12  grammes,  while  the  normal  quantity  of  indican  in- 
creased tenfold.  In  a  case  of  cancer  of  the  liver,  Hirne  found 
the  proportion  of  urea  as  low  as  from  6  to  7  grammes  in  700 
grammes  of  urine.  In  cholera,  where  the  coldness  of  the  body 
and  general  collapse  indicate  an  arrest  of  the  vital  functions 
and  diminished  oxidation  of  tissue,  there  is  a  notable  diminution 
of  urea  and  other  extractive  matters  of  a  lower  form  of  oxida- 
tion. In  a  case  of  this  description  Desnos  and  Chalvet  found 
but  traces  of  urea  with  4  per  1,000  extractive  matter.  In  the 
blood  of  the  same  patient  urea  existed  in  the  proportion  of  3*6  per 
1,000,  and  extractive  matter  19  per  1,000.  During  the  period  of 
reaction  the  patient  eliminated  700  grammes  of  urine  in  twenty  - 
four  hours,  and  the  urea  amounted  to  28*8  per  1,000,  and  the 
extractive  matter  to  22.  It  is  inferred  that  the  collapse  in  this 
disease  may  be  due  to  the  retention  in  the  blood,  to  some  extent, 
of  the  urea  and  extractive  matter,  and  that  the  conditions  may 
have  some  etiological  relationship  with  uraemia.  The  sweats 
which  supervene  in  cholera  during  the  period  of  reaction  contain, 
as  well  as  the  urine,  a  large  quantity  of  urea,  which  had  been 
retained  in  the  blood  by  the  ischuria.  On  spontaneous  evapora- 
tion of  the  cutaneous  transudation,  a  white  crystalline  powder 
of  urea  forms.  In  dropsy  the  proportion  of  urea  in  the  urine 
is  notably  diminished;  but  it  is  contained  in  the  fluid  effused 
into  the  various  cavities  and  tissues  of  the  body.  In  these 
cases,  under  the  influence  of  diuretics,  urea  appears  in  large 
quantity  in  the  urine.  Urea  is  found  in  the  fluid  of  hydrocele 
to  the  extent  of  25*62  grm.  per  litre  ;  and  in  dropsy  the  blood  may 
be  found  to  contain  0*365  grm.  per  litre,  against  0*18  to  0  20, 
the  normal  quantity.  In  uraemia,  that  the  diminution  of  urea  is 
due  to  deficient  oxidationf  of  tissue  is  shown  by  the  greatly 
diminished  temperature  of  the  body.  It  is  not  clear,  nor  even 
probable,  that  the  symptoms  of  uraemia  are  exclusively  due  to 
the  retention  of  urea  in  the  blood,  but  rather  to  other  excremen- 

*  Revue  des  Sciences  Med.,  1873,  and  Virchow's  Archiv.,  Bd.  lvi. 
t  Vide  'Lectures  on  Bright' s  Disease,'  by  Author  (Churchills). 


68  THE  URINE  IN  HEALTH  AND  DISEASE. 


titious  elements  which  have  not  yet  been  isolated.  Urea  maybe 
injected  with  impunity,  in  considerable  doses,  into  the  blood.  In 
certain  cases  of  albuminuria  it  is  well  known  that  there  is  a  con- 
siderable diminution  of  urea.  This  seems  to  be  due  to  arrested 
elimination,  as  well  as  to  deficient  formation.  Into  the  latter 
question  we  cannot  enter  here,  but  on  the  former  it  may  be 
remarked  that  this  is  characteristic  of  the  '  small  red  granular 
kidney.'*  In  this  condition  we  have  large  hyaline  tube  casts  in 
the  urine,  which  indicate  that  the  convoluted  tubes  have  been 
denuded  of  their  epithelium,  whose  special  function  it  is  to 
separate  the  urinary  solids ;  and  hence  we  have  a  low  specific 
gravity  of  urine  (1010  to  1005),  and  urea  and  extractive  matter 
accumulating  in  the  blood. 

Uraemia. — MM.  Grehant  and  Quinquand  have  returned  to  the 
investigation  of  this  subject  by  experimenting  on  animals. 
Subcutaneous  injections  of  aqueous  solutions  of  pure  urea  were 
employed  in  gradually  increasing  quantities  on  frogs,  guinea-pigs, 
rabbits,  pigeons  and  dogs.  The  result  was  constant  for  the 
different  kinds  of  animals,  and  consisted  in  a  more  or  less  rapid 
death  from  tetanic  convulsions,  similar  to  those  produced  by 
strychnia.  The  most  numerous  experiments  were  performed  on 
dogs.  The  toxic  dose  of  urea  in  the  blood  was  fixed  with  exacti- 
tude, and  the  influence  of  urea  on  muscular  contractility  was 
studied.  Death  always  ensued  when  a  dog  received  into  its 
system  10  grammes  of  urea  for  every  kilogramme  of  body 
weight.  The  proportion  of  urea  in  the  blood,  as  estimated  just 
before  or  after  death,  was  0*6  gramme  for  every  100  grammes  of 
blood,  and  this  relative  proportion  obtained  in  all  other  animals 
employed.  In  a  case  of  azuria  in  a  man,  the  proportion  was 
•410  per  100  grammes,  and  in  another  case  of  retention  of  urine 
•278  ;  in  a  case  of  interstitial  nephritis,  the  patient  suffering  from 
uraemic  dyspnoea,  it  was  *210,  and  in  a  case  of  uraemic  coma  *215. 
Under  the  circumstances  of  the  experiments  all  the  tissues  of  the 
animals  were  impregnated  with  urea,  so  that  100  grammes  of 
blood  yielded  613  milligrammes  of  urea  ;  100  grammes  of  liver, 
580  milligrammes ;  100  grammes  of  cardiac  tissue,  311  milli- 
grammes ;  100  grammes  of  spleen,  662  milligrammes.  The 
*  Vide  1  Lectures  on  B right's  Disease,'  by  Author  (Churchill's). 


NORMAL  ELEMENTS  OF  THE  URINE. 


69 


observers  always  noticed  that  the  urea  injected  under  the  skin 
was  never  completely  absorbed,  even  at  the  time  of  death,  though 
death  might  have  been  delayed  for  ten  hours.  They  also  found 
that  urgemia  does  not  increase  nor  diminish  muscular  contrac- 
tility. The  blood  of  dead  animals,  when  submitted  to  distillation 
at  a  temperature  of  40°  C.  in  vacuo,  furnished  a  liquid  absolutely 
free  from  ammonia ;  the  conclusion  drawn  from  the  experiment 
is  that  urea  does  not  act  as  ammonic  carbonate.  On  the  whole, 
it  appears  that  leucomaines,  ptomaines  and  other  extractives 
participate  in  the  production  of  uraemia. 

Medicinal  Agents  which  influence  the  Excretion  of  Urea. 
— The  medicinal  agents  which  influence  the  excretion  of  urea 
are  divisible  into  two  groups,  viz  ,  those  which  increase,  and 
those  which  diminish,  the  amount  of  urea.  These  substances 
may  be  thus  tabulated  : 


Medicinal  Agents  which  in- 

Medicinal Agents  which  di- 

crease the  Amount  of  Urea. 

minish  the  Amount  of  Urea. 

Urea  itself. 

Digitalis. 

Uric  acid. 

Alcohol. 

Common  salt. 

Coffee.     [  f 

Phosphoric  acid. 

Tea.  J 

Squill. 

Iodide   of  potassium  and 

Glycin. 

sodium. 

Leucin. 

Bromide  of  potassium. 

Theobromine. 

Arsenic. 

Colchicum.* 

Turpentine. 

Cubebs. 

Nitrate  of  potash  and  soda. 

Atropine. 

Alkaline  carbonates. 

Cantharides. 

Mercury. 

Vegetable  acids. 

Antipyrin. 

Ferruginous  preparations. 

Valerian. 

Hypophosphite  of  soda. 

Sulphate  of  quinine. 

Chloride  of  potassium. 

Benzoic  acid. 

Chloride  of  ammonium. 

Coca. 

Permanganate  of  potash. 
Large  quantities  of  water. 

Oxygen. 

*  Vide  Author's  '  Observations  on  Therapeutics  and  Disease ' 
(Churchills). 

t  1  Aliments  d'epargne.' 


70 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


Therapeutic  Indications. — If  an  excessive  excretion  of  urea 
indicate  a  preternatural  disintegration  of  nitrogenous  tissue,  and 
the  system  appear  to  suffer  thereby,  then  a  diet  rich  in  nitrogen 
is  indicated,  such  as  animal  soups,  eggs,  milk,  etc.,  and  one  or 
other  of  the  moderators  of  disintegration  above  tabulated.  In 
health  a  farinaceous  diet,  such  as  arrowroot,  sago,  tapioca,  etc., 
will  diminish  the  amount  of  urea.  Should  it  appear  that  too 
little  urea  is  formed  by  the  system,  then  exercise  ought  to  be 
enjoined  in  order  that  more  oxygen  may  be  inhaled,  and  one  of 
the  group  of  exciters  of  metamorphosis  administered,  such  as 
preparations  of  iron,  common  salt,  permanganate  of  potash,  etc. 


Carbon  ... 
Hydrogen 
Nitrogen 
Oxygen  ... 
Water    . . . 


UKIC  ACID. 

C5H4N403  =  168. 


33-714 
1-191 
33-333 
19-048 
10-714 


100-000 


Natural  State — Extraction  and  Preparation  of  Uric  Acid — Properties 
of  Uric  Acid — Urates— Acid  Sodium  Urate  —  Acid  Potassium 
Urate  —  Acid  Ammonium  Urate  —  Acid  Calcium  Urate  —  Acid 
Magnesium  Urate— Lithium  Urate — Tests  for  Uric  Acid — Quantita- 
tive Estimation  of  Uric  Acid — Uric  Acid  in  Albuminous  Urine — 
Extraction  of  Uric  Acid  from  Calculi  and  Sediments — Physio- 
logical Relations  of  Uric  Acid  —  Pathology  of  Uric  Acid — 
Therapeutic  Indications. 

Natural  State. — After  urea,  uric  acid  is  the  most  important 
normal  element  of  the  urine.  It  is  found  in  all  animals,  even 
the  lowest  in  the  scale.  Griffiths  has  found  it  in  the  green  gland 
of  the  cray-fish ;  and  MacMunn  in  the  Malpighian  tubes  of 
insects  and  the  nephridia  of  snails.  Mettlebach  found  from 
8  to  45  milligrammes  of  uric  acid  per  100  c.c.  of  urine  in  oxen. 
The  statement  is  therefore  inaccurate  that  it  is  absent  in  the 
urine  of  herbivorous  animals,  and  is  here  replaced  by  hippuric 
acid.    The  urine  of  birds  contains  a  largo  (mantity  of  uric  acid, 


NOEMAL  ELEMENTS  OF  THE  URINE. 


71 


and  that  of  serpents  is  almost  entirely  composed  of  pure  uric 
acid.  The  urine  of  man  contains  a  few  decigrammes  per  diem. 
The  blood  contains  it  to  a  like  amount,  and  here  the  proportion 
is  largely  augmented  in  cases  of  gout.  It  is  likewise  in  all 
probability  the  materies  morbi  of  rheumatism;  and  everything 
points  to  its  being  a  product  of  suboxidation,  as  arising  from  an 
excessive  proteid  dietary,  alcoholic  and  vinous  indulgences, 
sedentary  habits,  and  all  such  conditions  as  retard  eremacausis, 
either  directly  or  indirectly.  It  is  found  either  free  or  as  urate 
of  soda  in  the  articular  concretions  of  gout  and  in  calculi.  In 
conformity  with  what  has  been  just  remarked,  it  is  reduced  in 
amount*  by  active  exercise  in  the  open  air,  by  the  inhalation  of 
oxygen,  by  lime-juice,  alkaline  carbonates,  and  vegetable  acids 
(which  are  in  the  system  converted  into  carbonates),  by  large 
doses  of  quinine,  by  common  salt,  by  salicylates  and  benzoates 
of  soda,  salts  of  lithium,  and  notably  by  colchicum,  by  which  it 
is  converted  into  urea.  It  may  be  obtained  for  purposes  of 
study  from  guano,  or  the  excrement  of  serpents,  from  uric  acid 
calculi,  or  from  urine. 

Extraction  and  Preparation.— Uric  acid  exists  in  the  urine 
especially  in  the  form  of  an  alkaline  urate.  It  is  sometimes 
spontaneously  deposited,  in  consequence  of  the  reactions  which 
accompany  the  cooling  of  urine  ;  it  is  then  more  or  less  coloured. 
In  order  to  extract  uric  acid  from  urine,  about  20  c.c.  of  hydro- 
chloric acid  are  added  to  a  litre  of  urine,  and  the  fluid  is  filtered. 
The  urates  are  thus  decomposed.  The  filtrate  being  allowed  to 
stand  for  twenty-four  hours,  a  precipitate  of  uric  acid  is  found  to 
have  deposited  on  the  bottom  of  the  vessel.  The  precipitate  is 
less  coloured  than  that  which  spontaneously  deposits  in  the 
urine ;  still,  it  presents  the  appearance  of  cayenne  pepper.  In 
order  to  obtain  crystals  in  a  state  of  purity,  the  crystals  obtained 
as  above  are  dissolved  in  sulphuric  acid,  and  then  precipitated 
with  water,  when  small  characteristic  crystals  of  great  whiteness 
are  obtained.  If  the  urine  be  of  low  specific  gravity,  it  is  well  to 
concentrate  it  by  evaporation  before  treatment  with  the  hytho- 
chloric  acid. 

*  Vide  '  Observations  on  Therapeutie3  and  Disease,'  by  D.  Campbell 
Black,  M.D.,  etc.  (J.  and  A.  Churchill). 


72 


THE  URINE  IN  HEALTH  AND  DISEASE. 


Properties  of  Uric  Acid. — Thus  prepared,  uric  acid  is  found 
to  be  a  weak  dibasic  acid,  which  furnishes  both  acid  and  neutral 
salts.  The  neutral  salts  are  more  soluble  than  its  acid  salts.  It 
presents  the  appearance  of  light  scales,  soft  to  the  touch,  and  of  a 
great  variety  of  forms  of  crystallization.  The  rhombic  form,  with 
two  obtuse  angles,  is  the  predominating  crystalline  form  of  uric 
acid.  These  crystals  are  often  designated  the  1  lozenge  '  form  of 
uric  acid.  A  '  dumb-bell '  form  is  also  described,  which  frequently 
exists  in  sediments.    It  is  well  to  note  that  oxalate  and  carbonate 


Fig.  17. — Typical  forms  ok  Ukic  Acid  Crystals. 

of  lime  present  the  same  form  of  crystallization.  Few  substances 
present  a  greater  variety  of  forms  than  uric  acid.  This  acid  has 
neither  taste  nor  odour,  and  it  does  not  redden  litmus.  It  is  very 
insoluble  in  water,  requiring  from  1,800  to  1,900  times  its  weight 
of  cold  water,  and  1,400  to  1,500  of  boiling  water,  to  dissolve  it. 
It  is  insoluble  in  alcohol  and  in  ether.  It  dissolves  easily  in  a 
solution  of  phosphate  of  soda,  in  lixed  alkalies,  in  carbonates, 
phosphates,  and  borates  of  the  fixed  alkalies,  but  not  in  the 
corresponding  ammoniacal  salts.  It  dissolves  with  difficulty  in 
ammonia.  Sulphuric  acid  dissolves  it  without  decomposition, 
and  it  may  be  precipitated  therefrom  by  the  addition  of  water. 
Nitric  acid  dissolves  it,  but  decomposes  it  in  so  doing.  A 


♦ 


NORMAL  ELEMENTS  OP  THE  URINE. 


73 


potassic  solution  of  uric  acid  reduces  Fehling's  solution,  and  may 
thus  be  confounded  with  glucose.  Heated  in  a  tube,  uric  acid 
decomposes  into  urea  and  cyanuric  acid.  It  forms  at  the  same 
time  hydrocyanic  acid  and  carbonate  of  ammonia.  Boiled  with 
acetate  of  lead,  uric  acid  is  decomposed  into  carbonic  acid> 
allantoi?ie,  ttrea,  and  oxalic  acid. 


Fig.  18.— Rarer  Forms  of  Uric  Acid  Crystals. 

If  one  part  of  uric  acid  be  treated  with  four  parts  of  con- 
centrated nitric  acid,  there  is  decomposition  with  effervescence, 
and  the  liquid  solidifies.  The  following  represents  the  decom- 
position which  takes  place  : 

2C5H4N403 + 2H20  +  02=2C4H2N204+2CO(NH2)2. 
uric  acid  alloxan  urea 

Uric  acid  may  be  decomposed  by  carbonic  acid,  a  fact  which 
accounts  for  the  presence  of  acid  urates,  and  their  deposition  in 
the  urine.  Alloxan  which  originates  as  above  is  remarkable  for 
the  beautiful  red  coloration  which  it  gives  with  ammoniacal 
vapour.  This  is  due  to  the  formation  of  iso-alloxanate  of 
ammonia  which  characterizes  uric  acid  (murexide  reaction).* 
By  the  action  of  caustic  potash  this  coloration  changes  to  purple - 

*  From  murex,  a  shell- fish  of  similar  tint. 


74 


THE  UEINE  IN  HEALTH  AND  DISEASE. 


blue.  All  the  urates  give  the  rnurexide  reaction.  As  with 
uric  acid,  the  urates  do  not  affect  litmus. 

Urates. — Uric  acid  forms  with  alkalies  two  series  of  salts — 
viz.,  the  neutral  urates  and  the  acid  urates,  which  are  much 
more  soluble  than  the  free  acid,  and  dissolve  more  easily  in  a 
hot  than  in  a  cold  solution.  Further,  the  neutral  salts  are  more 
soluble  than  the  acid  salts ;  neutral  urates  of  potassium  and 
lithium  are  the  most  soluble,  and  acid  urate  of  ammonia  the 
least  soluble.  When  hydrochloric  or  acetic  acid  is  added  to 
urine  for  the  purpose  of  decomposing  the  urates,  the  uric  acid 
separates  in  a  crystalline  form ;  and  if  the  fluid  is  concentrated 
this  takes  place  immediately,  but  if  diluted  a  considerable 
interval  will  elapse  before  precipitation. 

Uric  acid,  being  very  insoluble  in  water,  does  not  exist 
normally  in  the  urine  as  such,  but  is  always  found  in  combina- 
tion in  the  form  of  acid  sodium  urate,  acid  potassium  urate, 
acid  ammonium  urate,  and,  under  rare  circumstances,  acid 
calcium  urate. 

Acid  sodium  urate  (C5H3NaN403). — This  constitutes  the 
most  common  urate  deposit,  and  presents  a  rose-colour  when 


Fig.  19.— Groups  of  Acicular  Crystals  and  Spherical  Masses  of 
Sodium  Urate. 

it  deposits  in  urine  which  has  become  cool.  It  is  rendered 
soluble  by  the  least  elevation  of  temperature.  Acid  urate  of 
sodium  is  soluble  in  about  1,200  parts  of  cold  water,  and  in  125 


NORMAL  ELEMENTS  OF  THE  URINE. 


75 


parts  of  boiling  water.  Under  the  microscope,  it  presents  the 
appearance  of  spherical  granules,  which  are  more  frequently 
in  clusters  than  singly.  With  nitric  acid  and  ammonia,  this 
salt  gives  the  murexide  reaction,  and  calcination  leaves  a 
residue  of  carbonate  of  soda. 

Acid  Potassium  Urate  (C5H3KN403). — This  urate  is  almost 
always  found  in  combination  with  that  of  soda,  and  is  more 
soluble  in  water.  One  gramme  dissolves  in  800  parts  of  water 
at  15°  C,  and  in  75  of  boiling  water.  It  leaves  on  calcination  a 
residue  of  carbonate  of  potash. 

Acid  Ammonium  Urate  (C5H3(NH4)N403). — This  urate  is  in- 
variably found  in  urine  which  has  become  ammoniacal.  It  is 
very  insoluble,  1  part  requiring  1,600  parts  of  water  for  its 
solution.  It  leaves  no  residue  on  calcination.  It  is  distinguish- 
able from  uric  acid  by  the  evolution  of  ammonia  when  heated 
with  caustic  soda.  It  presents  the  appearance  of  spheres,  more 
or  less  voluminous,  sometimes  spiney.  Two  spheres  are  some- 
times united  by  a  peduncle,  and  thus  present  a  dumb-bell 
appearance. 


Fig.  20. — Ammonium  Urate. 


Acid  Calcium  Urate. — This  form  of  urate  is  found  much  more 
rarely  in  the  urine.  It  is  frequently  found  in  calculi.  On 
calcination  it  leaves  a  residue  of  carbonate  of  lime.  It  is  very 
insoluble  in  water.  It  effervesces  with  acids,  and  gives  in 
solution  the  reaction  of  the  salts  of  lime. 

Acid  Magnesium  Urate  is  sometimes  found  in  the  urine 


76 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


under  similar  circumstances.  In  solution  it  gives  with  acids  the 
reactions  of  magnesium  salts. 

Urate  of  Lithium,  the  most  soluble  of  all  the  urates,  is 
sometimes  found  in  urine.  It  dissolves  in  116  times  its  weight 
of  water  at  39°  C,  and  in  367  parts  of  water  at  20°  C.  The 
salts  of  lithium  are  thus  used  therapeutically  as  eiiminants  of 
uric  acid.* 

In  winter,  owing  to  the  cold,  urates  are  found  most  frequently 
in  the  urine.  When  the  urine  is  very  acid,  from  containing  a 
large  proportion  of  acid  phosphates,  these  appropriate  from  the 
neutral  urates  a  portion  of  their  base,  and  thus  transform  them 
into  acid  urates,  which  being  less  soluble  than  the  neutral,  are 
precipitated.  Indeed,  the  acid  phosphates  may  remove  the 
whole  of  the  base,  and  thus  precipitate  free  uric  acid.  Hence 
the  formation  of  deposits  of  urates  and  uric  acid  during  the  first 
period  of  the  decomposition  of  urine  on  exposure  to  air.  When 
heated,  all  the  urates  dissolve,  and  also  on  addition  of  caustic 
soda  or  potash,  and  when  treated  with  acids  they  yield  uric  acid 
crystals.  Corresponding  to  these  acid  urates,  there  are  the 
normal  urates  of  ammonium,  sodium,  potassium,  calcium,  and 
lithium.  Being  much  more  soluble  than  the  acid  urates,  they 
remain  in  solution  when  precipitation  of  the  latter  takes  place. 
The  formation  of  carbonic  acid  in  the  urine  may  occasion  the 
change  from  neutral  to  acid  urates  thus : 

2C5,H2,Na2,N4O3+H20  +  CO2=2C5,H3.NaN4,O3-fNa2,CO3. 
normal  sodium  urate  acid  sodium  urate 

Tests  for  Uric  Acid. — Uric  acid  is  recognisable  by  its 
characteristic  microscopic  appearances.  If  but  a  small  quantity 
of  fluid  be  available,  from  2  to  3  grammes  are  placed  in  a 
test-tube  with  two  or  three  drops  of  a  solution  of  glacial 
acetic  acid,  a  piece  of  linen  of  from  3  to  4  c.c.  in  length  is 
immersed  in  it,  and  the  fluid  is  allowed  to  repose  in  a  cool 
place  for  about  twenty-four  hours.    The  uric  acid  is  found  to 

*  Saturation  of  the  urine  with  ammonium  chloride  precipitates  all 
the  urates.  The  murexide  test  can  then  be  applied,  and  the  quantity 
of  uric  acid  in  a  given  specimen  of  urine  can  thus  be  estimated  by 
weighing. 


NORMAL  ELEMENTS  OF  THE  URINE. 


77 


have  deposited  on  the  linen,  and  the  microscopic  examination 
may  then  be  made.  It  may  also  be  separated  by  evaporating  a 
small  quantity  of  urine  to  dryness  in  a  water-bath,  any  albumen 
having  been  previously  removed.  The  residue  is  then  treated 
with  alcohol,  to  remove  the  urea  and  other  constituents  soluble 
therein.  Then  the  fluid  is  treated  with  weak  hydrochloric 
acid  to  remove  the  salts,  and  the  uric  acid  alone  remains. 
The  result  of  microscopic  examination  may  be  confirmed  by 
chemical  tests.  Thus,  in  a  small  porcelain  capsule  a  little  of 
the  sediment,  or  of  the  residue  obtained  as  above,  is  placed,  and 
moistened  with  a  drop  or  two  of  nitric  acid.  The  uric  acid 
dissolves  with  effervescence,  giving  off  reddish  vapours.  Moderate 
heat  is  then  applied  to  volatilize  the  excess  of  acid,  a  reddish- 
coloured  residue  being  the  result,  and  one  or  two  drops  of  a  solu- 
tion of  ammonia  added  (1  gramme  of  ammonia  to  9  grammes  of 
water),  when  a  purple  coloration  is  obtained,  which  constitutes  the 
murexide  test  (ammonium  purpurate — C8H4(NH4)N506).  The 
same  result  is  obtained  by  exposure  to  ammoniacal  vapour.  The 
addition  of  caustic  potash  or  soda  causes  a  violet-blue  colora- 
tion. 

According  to  Magnier  de  la  Source,  the  reaction  may  be  better 
accomplished  in  the  following  manner :  Instead  of  employing 
nitric  acid,  a  few  drops  of  bromine  water  (5  or  6  drops  of 
bromine  to  100  c.c.  of  water)  are  added  to  the  residue  operated 
on,  and  the  whole  evaporated  on  a  water-bath.  The  ammonia  is 
then  added,  when  a  purple  coloration,  which  on  the  addition  of 
potash  passes  into  a  violet-blue,  is  the  result.  These  tests  are 
of  extreme  delicacy. 

Scliijfs  Test. — A  little  of  the  residue  is  dissolved  in  sodium 
carbonate,  and  a  drop  of  the  solution  is  then  placed  on  a  piece 
of  filter-paper,  previously  moistened  with  a  solution  of  nitrate  of 
silver,  when  a  brownish  stain  is  produced,  due  to  deposition  of 
metallic  silver. 

Bosenberg's  Beaction. — If  an  equal  volume  of  a  solution  of 
phosphotungstic  acid  be  added  to  urine,  with  a  drop  of  caustic 
potash,  soda,  or  ammonia,  a  blue  coloration,  due  to  the  presence 
of  uric  acid,  results  (Pharm.  Centralhalle,  xxxi.,  1890). 

Beaction  of  Dietrich. — If  a  little  uric  acid  solution  be  added  to 


78  THE  URINE  IN  HEALTH  AND  DISEASE. 

an  iodized  solution  of  hypochlorite  of  sodium  a  rose  coloration 
is  produced,  which  disappears  if  the  sodium  solution  be  in 
excess. 

If  an  alkaline  solution  of  uric  acid  or  of  urates  be  heated  with 
the  liquor  of  Barriswell,*  a  white  precipitate  of  urate  of  copper 
and  a  red  precipitate  of  urate  of  copper  (cuprosum)  result.  This 
precipitate  must  not  be  confounded  with  the  precipitate  similarly 
caused  by  glucose. 

If  a  solution  of  uric  acid  in  caustic  soda  be  boiled  with  a  small 
amount  of  Fehling's  reagent,  a  grayish  precipitate  of  urate  of 
cuprous  oxide  is  obtained.  Should  the  copper  salt  be  in  excess, 
a  red  cuprous  oxide  is  the  result. 

Quantitative  Estimation  of  Uric  Acid. — Empirically,  a 
rough  estimate  of  the  amount  of  uric  acid  in  urine  may  be 
obtained  by  multiplying  the  two  last  figures  of  the  density  by  2, 
when  the  result  would  express  in  centigrammes  the  quantity 
of  uric  acid  per  litre.  While  the  process  is  somewhat  trouble- 
some, weighing  alone  gives  the  most  accurate  quantitative 
results.  For  this  purpose  the  acid  is  precipitated  as  above  by 
hydrochloric  acid,  and  collected  after  sufficient  repose  in  a  cool 
place.  One  hundred  c.c.  of  filtered  urine  (any  albumen  having 
been  removed)  are  placed  in  a  porcelain  capsule,  and  3  to  4 
per  cent,  of  hydrochloric  acid  added  ;  after  from  twenty-four  t© 
thirty  hours'  repose  the  crystals  are  collected  on  a  filter,  whose 
tare  has  been  obtained.  The  uric  acid  is  washed  with  distilled 
water,  which  process  is  continued  until  the  wash-water  is  no 
longer  acid.  The  uric  acid  is  then  to  be  washed  with  alcohol 
to  remove  hippuric  acid  and  any  accidental  colouring  matters. 
It  is  then  dried  at  a  temperature  of  100°  C.  until  it  ceases  to  lose 
weight ;  from  the  final  weighing  the  weight  of  the  filter  is 
deducted,  the  result  being  the  weight  of  uric  acid.  Uric  acid  is 
not  absolutely  insoluble  in  water,  nor  in  water  acidulated  with 
hydrochloric  acid.  Hence  to  obtain  perfect  accuracy  of  result, 
an  allowance  must  be  made  for  the  portion  dissolved  by  adding 
0'0045  grm.  for  each  c.c.  of  water  employed  in  washing. 

Haycraft's  Method.— This  process  requires  (1)  a  centinormal 

*  Cupro-potassic  liquor. 


NORMAL  ELEMENTS  OF  THE  URINE. 


79 


solution  of  sulpho cyanide  of  potassium,  to  obtain  which 
8  grammes  of  this  salt  are  dissolved  in  a  litre  of  water  :  1  c.c. 
two  =  0*00168  of  uric  acid  ;  (2)  a  decinormal  solution  of  nitrate  of 
silver ;  (3)  a  saturated  solution  of  iron  alum  ;  (4)  a  20  to  30  per 
cent,  solution  of  nitric  acid;  (5)  a  solution  of  ammonia;  and 
(6)  an  ammoniacal  solution  of  nitrate  of  silver,  to  obtain  which 
5  grammes  of  nitrate  of  silver  are  dissolved  in  100  c.c.  of  water,  a 
sufficiency  of  ammonia  being  added  to  produce  a  limpid  solu- 
tion. 

Process. — To  25  c.c.  of  urine  containing  no  albumen  add 
1  gramme  of  sodium  bicarbonate,  and  from  2  to  3  c.c.  of  the 
ammoniacal  solution ;  then  add  from  1  to  2  c.c.  of  the  silver 
solution,  in  order  to  precipitate  the  uric  acid  as  urate  of  silver. 
Wash  the  precipitate  with  distilled  water  in  order  to  remove  the 
excess  of  the  soluble  silver  salt ;  dissolve  the  precipitate  in  a  few 
c.c.  of  nitric  acid  solution,  and  precipitate  the  silver  with  the 
solution  of  sulphocyanide  of  potassium,  the  iron  alum  serving 
as  an  indicator,  the  number  of  c.c.  of  y|ro  of  the  sulphocyanide 
solution,  multiplied  by  0*00168  gramme,  indicating  the  quantity 
of  uric  acid. 

This  process  is  based  on  the  precipitation  of  uric  acid  in  a 
state  of  urate  of  silver,  insoluble  in  ammonia  and  soluble  in 
nitric  acid.  Hay  craft  attributes  the  irregularity  of  the  com- 
position of  urate  of  silver,  as  indicated  by  Salkowski,  in  part  to 
the  precipitation  of  ammonio-phosphate  of  magnesium,  and  in 
part  to  the  reduction  of  the  silver,  which  varies  with  time  and 
temperature. 

Salkowski-Ludwig  Method. — If  an  ammoniacal  solution  of 
nitrate  of  silver  be  added  to  a  solution  of  uric  acid,  to  which  has 
been  previously  added  an  ammoniacal  mixture  of  chloride  of 
magnesium  and  of  chloride  of  ammonium,  the  uric  acid  is 
precipitated  as  a  magnesio-silver  salt.  This  is  collected,  washed, 
and  decomposed  by  either  sodium  or  potassium  hydrosulphide, 
when  the  uric  acid  again  passes  into  solution  as  a  urate  of  the 
alkali.  When  an  excess  of  hydrochloric  acid  is  added  to  this 
solution,  the  urate  is  decomposed;  the  uric  acid  is  separated  out, 
and  may  thus  be  collected  and  weighed. 

Process  of  Bayrac. — Of  the  nitrogenous  compounds  of  the 


80 


THE   URINE  IN  HEALTH  AND  DISEASE. 


urine,  urea,  uric  acid,  and  creatinine  are  alone  decomposed  by 
hypobromite  of  soda,  evolving  their  nitrogen  incompletely  in 
the  cold;  and  completely  on  being  heated.  The  other  nitro- 
genous constituents  exist  in  urine  in  so  small  an  amount  as  not 
to  merit  consideration.  The  principle  of  this  process  consists 
in  separating  the  uric  acid  from  the  two  other  nitrogenous  con- 
stituents by  means  of  alcohol,  and  in  acting  on  the  isolated 
principle,  by  means  of  a  concentrated  solution  of  hypobromite  of 
soda,  at  a  temperature  of  from  90°  to  100°  C.  Fifty  c.c.  of  urine 
are  concentrated  on  a  water-bath,  the  uric  acid  precipitated 
by  5  c.c.  or  10  c.c.  of  dilute  hydrochloric  acid,  and  washed 
with  alcohol.  This  removes  the  creatinine,  and  the  urea, 
leaving  the  uric  acid ;  the  acid  is  then  dissolved  on  a  water-bath 
by  20  drops  of  caustic  soda,  and  treated  with  15  c.c.  of  a 
concentrated  solution  of  hypobromite  of  soda,  at  a  temperature 
of  from  90°  to  100°  C.  {Journal  de  Pharmacie  et  de  Chimic, 
xxi.,  1890,  p.  611). 

Of  other  processes  for  the  quantitative  analysis  of  uric  acid 
may  be  mentioned  those  of  Arth*  and  Butte. f 

Uric  Acid  in  Albuminous  Urine.— When  the  urine  con- 
tains albumen,  as  hydrochloric  acid  precipitates  this  body,  it  is 
necessary  to  employ  a  6  per  cent,  solution  of  phosphoric 
acid,  or  an  equal  volume  of  glacial  acetic  acid,  which  pre- 
cipitates the  uric  acid  to  the  exclusion  of  the  albumen.  In 
the  case  of  a  more  or  less  considerable  quantity  of  urine,  the 
albumen  may  be  coagulated  by  heat,  and  thus  separated  by 
pouring  on  a  filter.  The  filtrate,  plus  the  water  employed  to 
wash  the  albumen  coagulum,  being  mixed  and  concentrated  if 
necessary,  the  amount  of  uric  acid  may  be  determined  in  the 
ordinary  manner. 

If  a  precipitate  of  urate  or  of  free  acid  has  already  formed  in 
a  vessel,  it  must  be  vigorously  agitated,  and  be  rapidly  poured 
into  another  vessel,  a  few  drops  of  caustic  soda  being  added  to 
cause  solution,  and  then  the  whole  is  filtered  ;  the  filtered  liquid, 
being  exactly  measured,  is  employed  for  the  determination  of 
the  uric  acid  and  the  albumen.    Instead  of  the  soda  solution 

*  Comp.  Rend,  de  VAcad.  des  Sciences,  February  17,  1890. 
f  Repertoire  de  Pharmacie^  1890,  p.  38. 


NORMAL  ELEMENTS  OF  THE  URINE. 


81 


a  gentle  heat,  not  sufficient  to  coagulate  the  albumen,  may  be 
employed  to  dissolve  the  urate  deposit. 
Extraction  of  Uric  Acid  from  Calculi  and  Sediments. — 

The  calculi  or  sediments,  finely  pulverized,  are  dissolved  in 
caustic  potash,  and  after  filtration  the  solution  is  acidified  with 
hydrochloric  acid.  The  uric  acid  is  again  dissolved  in  caustic 
potash  and  reprecipitated  by  the  acid,  until  the  product  obtained 
be  sufficiently  pure.  Instead  of  treating  the  potash  solution  with 
hydrochloric  acid,  M.  Mehu  advises  the  passing  of  a  current  of 
carbonic  acid  gas  through  the  solution,  whereby  the  free  alkali 
becomes  a  carbonate,  while  the  uric  acid  is  deposited  in  the 
condition  of  a  urate  of  potash.  This  deposit  may  be  then 
collected,  carefully  washed,  and  decomposed  by  hydrochloric 
acid. 

Physiological  Eelations  of  Uric  Acid.— In  common  with 
urea,  uric  acid  results  from  the  metamorphosis  of  proteid  elements 
in  the  economy  ;  but  it  is  not  an  ultimate  product  of  combustion, 
for  when  introduced  into  the  system  it  undergoes  further  com- 
bustion, forming  urea.  The  quantity  of  uric  acid  eliminated  in 
twenty-four  hours  is  much  less  than  that  of  urea,  varying  from 
0*30  gramme  to  0*80  gramme,  or  an  average  of  0*55  gramme, 
or  about  one-tenth  of  the  solid  matters  of  the  urine.  This 
average  varies  according  to  circumstances.  A  proteid  diet 
augments  the  amount  of  uric  acid,  while  a  non-nitrogenous 
dietary  causes  a  diminution.  A  diminution  also  appears  after 
indulgence  in  copious  draughts.  The  greater  portion  of  the  uric 
acid  is  contained  in  the  urine  in  the  form  of  an  alkaline  urate  ; 
sometimes  the  urine  contains  uric  acid  in  a  free  state,  which 
separates  either  after  emission  of  the  urine,  owing  to  acid 
fermentation,  or  in  the  bladder.  In  all  quantitative  analyses  of 
uric  acid,  the  entire  urine  of  twenty-four  hours  must  be  operated 
upon,  owing  to  the  feeble  solubility  of  the  acid.  When  the 
proportion  of  uric  acid  in  the  body  may  be  quite  normal,  a  very 
little  diminution  in  the  urinary  secretion  may  suffice  to  cause  an 
abundant  precipitation. 

Pathology  of  Uric  Acid. — Uric  acid  is  excreted  in  augmented 
amount  in  all  febrile  affections,  accompanied  by  embarrassment 
of  respiration,  such  as  pleurisy,  pericarditis,  capillary  bronchitis, 

6 


82 


THE  UEINE  IN  HEALTH  AND  DISEASE. 


chronic  emphysema,  etc.,  there  being  obviously  in  these  circum- 
stances a  deficiency  of  oxidation.  The  same  thing  obtains  in 
laucocythaemia,  pernicious  anaemia,  and  in  the  constitutional 
condition  termed  the  uric  acid  diathesis,  the  cause  being 
evidently  the  same.  The  blood  being  poor  in  iron,  the  organic 
combustion  is  less  perfect.  In  the  uric  acid  diathesis  the  acid 
separates  in  the  urinary  passages,  and  is  eliminated  with  the 
urine  in  the  form  of  little  reddish  particles,  known  as  uric  acid 
gravel.  In  cases  of  articular  rheumatism,0  the  amount  of  uric 
acid  is  augmented  during  the  period  of  greatest  intensity  of  the 
fever,  and  diminishes  during  its  decline.  Its  amount  is  also 
diminished  in  chronic  rheumatism.  It  forms  concretions  of 
urate  of  soda  in  the  joints  in  gout ;  and  before  the  attack  its 
excretion  is  very  feeble,  while  after  the  attack  it  augments,  and 
finally  diminishes.  In  chronic  gout  a  diminution  is  observed. 
In  cases  of  obesity  and  diabetes  there  is  a  diminution  of  uric 
acid.  In  a  certain  form  of  glycosuria,  described  by  Bouchard  as 
glycojwlyuric  diabetes,  there  is,  on  the  contrary,  a  consider- 
able augmentation  of  this  body,  amounting  to  as  much  as  3 
grammes  per  diem,  during  which  period  the  sugar  diminishes  in 
quantity  or  totally  disappears.  In  cases  of  interstitial  nephritis, 
where  there  is  desquamation  of  the  cells  of  the  convoluted  tubes, 
there  is,  for  obvious  reasons,  a  diminished  amount  of  uric  acid. 
The  same  obtains  in  grave  cases  of  scarlet  fever.  In  cases  of 
typhoid  fever  the  appearance  of  uric  acid  or  of  urates  in  the 
urine  has  been  held  as  indicating  a  period  of  crisis.  According 
to  Bouchard,  in  cases  of  lead-poisoning  the  proportion  of  uric 
acid  is  diminished  to  about  a  half.  Haig  maintains  that  its 
presence  in  the  blood  augments  vascular  tension. 

Therapeutic  Indications. — If  an  excess  of  uric  acid  represent 
an  imperfect  oxidation  of  proteidsin  11  ie  body,  and  the  full  oxida- 
tion be  represented  by  urea,  then  the  dietary  should  be  regulated 
accordingly,  and  the  medicinal  agents  administered  should  be 
such  as  stimulate  and  augment  eremacausis.  Nitrogenous  diet 
should  be  restricted,  and  vegetable  and  farinaceous  diet  be 
enjoined.  Sulphate  of  quinine  diminishes  uric  acid,  as  likewise 
bicarbonates,  alkaline  carbonates,  and  vegetable  acids  (which  arc 
*  Vide  Author's  1  Observations  on  Therapeutics  and  Disease.' 


NORMAL  ELEMENTS  OF  THE  URINE. 


83 


converted  in  the  system  into  carbonates),  and  all  of  which  act  as 
energetic  oxidizing  agents.  Common  salt,  sulphate,  carbonate, 
salicylate,  and  benzoate  of  soda,  and  inhalations  of  oxygen*  act  in 
a  similar  manner.  The  administration  of  colchicum  is  indicated, 
for  there  is  sufficient  scientific  testimony  to  its  augmenting  the 
amount  of  urea  by  diminishing  and  transforming  uric  acid, 
which  it  appears  to  effect  in  the  liver.  The  salts  of  lithium 
cause  the  speedy  disappearance  of  uric  acid,f  and  piperazine 
is  said  to  possess  a  similar  property. 


HIPPURIC  ACID. 


Hippuric  Acid  (C9,H9N03)  is  found  especially  in  the  urine  of 
the  herbivora,  as  the  horse,  the  ox,  etc.  In  the  urine  of  the 
carnivora,  and  especially 
in  that  of  man,  it  exists 
in  but  a  very  minute 
quantity.  It  occurs  here, 
however,  after  the  inges- 
tion of  certain  vegetables, 
such  as  asparagus,  plums, 
whortle- berries,  brambles, 
and  generally  a  purely 
vegetable  diet,  and  from 
the  use  of  benzoic  acid, 
cinnamic  acid,  essence  of 
bitter  almonds,  quinine 
and  analogous  bodies.  Its 
presence  has  been  de- 
monstrated in  the  urine 
of  new-born  infants  for  some  days  after  birth.  Some  authors 
maintain  its  existence  in  the  blood,  in  the  suprarenal  capsules, 

*  Vide  Author's  1  Observations  on  Therapeutics  and  Disease.' 

j  Lithium  carbonate  dissolves  in  200  parts  of  boiling  water.  With 
an  equal  wt  ight  of  uric  acid  half  that  quantity  of  water  will  suffice 
even  at  the  temperature  of  the  b-idy.  The  uric  acid  eliminates  car- 
bonic a'iid  from  the  carb  nate.  Salts  of  lithium  are  consequently  pre- 
scribed in  cases  of  gout  and  the  uric  acid  diathesis. 


(a 


Fig.  21. — Hippuric  Acid. 
Rhombic  prisms  ;  (b)  needle  form. 


84 


THE  URINE  IN  HEALTH  AND  DISEASE. 


and  the  sweat,  but  this  is  doubtful.  In  the  urine,  hippuric  acid 
is  found  as  a  hippurate  of  soda  or  potash  (urine  of  the  horse). 
It  is  not  probable  that  it  exists  in  a  free  state  in  the  urine  in 
even  the  feeblest  proportion.  Hippuric  acid  is  colourless,  odour- 
less, and  of  a  slightly  bitter  taste ;  it  crystallizes  in  the  form 
of  rhomboidal  prisms,  with  pyramidal  ends,  and  sometimes  in 
the  form  of  fine  needles.  These  crystals  are  frequently  arranged 
in  groups,  and  present  a  semi-transparent  or  milky  appearance. 
They  dissolve  in  600  parts  of  cold  water,  and  in  a  much  smaller 
amount  of  boiling  water.  They  are  easily  soluble  in  alcohol  and 
insoluble  in  petroleum-ether,  and  may  be  thus  separated  from 
benzoic  acid,  which  is  soluble  in  this  reagent.  Solutions  of 
hippuric  acid  strongly  redden  litmus  paper. 

Hippuric  acid,  when  feebly  heated  in  a  test-tube,  is  transformed 
into  an  oily  fluid,  which  solidifies  on  cooling ;  at  a  higher 
temperature  the  mass  becomes  red,  and  evolves  benzoic  acid 
and  an  agreeable  odour  of  hay,  ultimately  becoming  of  the  odour 
of  hydrocyanic  acid.  When  it  is  evaporated  with  concentrated 
nitric  acid  it  evolves  an  odour  of  nitro-benzene.  Hippuric  acid 
is  monobasic  and  forms  salts,  with  the  exception  of  its  iron  salts, 
which  are  freely  soluble  in  water.  When  boiled  with  con- 
centrated mineral  acids,  or  heated  for  a  long  time  with  water  at 
a  temperature  of  170°  to  180°  C,  it  is  resolved  into  benzoic  acid 
and  glycocoll.  When  it  undergoes  the  alkaline  fermentation 
under  the  influence  of  the  Micrococcus  ureal,  the  same  change 
ensues.  Hence  it  is  not  found  in  putrid  urine,  where  its  place 
is  taken  by  benzoic  acid,  which  is  one  of  the  products  of  the 
change.  It  is  formed  in  the  body  by  the  union  of  benzoic  acid 
with  glycin  (glycocoll). 

Extraction. — To  extract  hippuric  acid,  the  following  is  the 
most  convenient  process:  Concentrate  on  a  water-bath  to  an 
eighth  of  its  volume  a  portion  of  the  fresh  urine  of  a  horse  ;  add 
hydrochloric  acid,  and  after  a  period  of  repose  the  hippuric  acid 
separates  in  fine  needles.  It  is  preferable,  however,  to  saturate 
the  fresh  urine  with  lime-water,  which  transforms  the  hippuric 
into  a  salt  of  lime  ;  the  fluid  is  then  filtered,  evaporated  to  a 
syrupy  consistence,  and  decomposed  by  hydrochloric  acid. 
Cazeneuve  recommends  that  a  litre  of  urine  be  evaporated  to  a 


NOEMAL  ELEMENTS  OF  THE  URINE. 


85 


tenth  of  its  volume,  or  100  grammes,  and  then  mixed  with 
200  grammes  of  '  plaster  '  (CaC03)  and  20  grammes  of  alum,  and 
dried  on  a  water-bath.  The  alum,  whose  reaction  is  acid,  decom- 
poses the  carbonates  and  sets  the  hippuric  acid  at  liberty.  The 
mixture  is  then  placed  in  a  digester  and  acted  upon  by  boiling 
ether,  which  dissolves  out  the  benzoic  acid  and  fatty  matter, 
and  leaves  crystals  of  hippuric  acid  of  great  brilliancy.  It  is 
easily  traced  in  the  urine  after  the  administration  of  benzoic 
acid. 

Tests  and  Quantitative  Analysis.— Submit  the  crystals 
obtained  as  above  to  microscopic  examination,  and  in  confirma- 
tion effect  the  above-mentioned  reactions.  Its  quantity  can  be 
determined  by  weighing  the  crystals. 

Meissner  advises  that  a  kilogramme  of  fresh  urine  be  operated 
on ;  add  to  it  a  solution  of  baryta  until  a  precipitate  is  obtained, 
filter,  and  to  the  filtered  fluid  add  drop  by  drop  dilute  sulphuric 
acid,  so  as  to  leave  no  trace  of  baryta.  Care  must  be  taken  not 
to  add  an  excess  of  sulphuric  acid.  Filter  anew,  and  exactly 
neutralize  with  hydrochloric  acid ;  evaporate  on  a  water-bath  to 
the  consistency  of  a  thick  syrup  ;  pour  into  a  wide -mouthed 
vessel  containing  200  c.c.  of  absolute  alcohol.  The  succinates 
and  the  chloride  of  sodium  precipitate,  and  the  hippuric  acid 
remains  in  solution.  After  agitation  and  prolonged  repose,  re- 
filter,  and  evaporate  the  alcohol  on  a  water-bath  ;  the  residue  is 
again  placed  in  a  wide-mouthed  bottle,  and  treated  with  hydro- 
chloric acid  and  about  125  grammes  of  slightly  alcoholized 
sulphuric  ether.  On  being  agitated  the  hippuric  acid  is  set  free, 
dissolving  in  the  ether,  and  may  be  precipitated  by  evaporation, 
and  then  dried  and  weighed.* 

Physiology  and  Pathology. — Hippuric  acid  is  found  in  normal 
human  urine  in  very  small  quantities — 0*30  gramme  to  1  gramme 
in  twenty-four  hours.  Its  amount  varies  according  to  alimenta- 
tion. After  the  ingestion  of  benzoic  acid  its  amount  is  aug- 
mented ;  on  a  flesh  dietary,  even,  it  may  appear  in  the  urine, 
being  derived  in  this  case  from  the  decomposition  of  proteids. 
The  change  from  benzoic  acid  into  hippuric  seems  to  be  effected 

*  One  or  two  drops  of  a  neutral  solution  of  ferric  chloride  give  a 
light  red  precipitate  with  hippuric  acid. 


86  THE  URINE  IN  HEALTH  AND  DISEASE. 

by  the  cells  of  the  convoluted  tubes.*  According  to  Salomon, 
after  the  excision  of  the  kidneys  in  rabbits  and  injection  of 
benzoic  acid  into  the  blood,  hippuric  acid  could  be  detected  in 
the  blood,  muscles,  and  liver  ;  on  the  other  hand,  in  diseases  of 
the  kidneys,  it  was  found  that  benzoic  acid  was  no  longer  capable 
of  being  transformed  into  hippuric  acid.  It  is  stated  that  even  in 
excised  kidneys  the  injection  of  benzoic  acid  is  followed  by  the 
appearance  of  hippuric  acid  in  the  blood  which  flows  from  the 
organ.  It  is  said  to  be  augmented  in  the  urine  in  diabetes  and 
chorea. 

Creatine  and  Creatinine. 

Creatine  (C4HyN302)t  exists  normally  in  muscular  tissue, 
both  striated  and  unstriated,  to  the  extent  of  2  per  cent.  The 
urine  does  not  normally  contain  creatine,  that  which  is  found  in 
it  originating  in  the  transformation  of  creatinine.  The  physio- 
logical role  of  creatine  is  undetermined.  It  does  not  seem  to  act 
as  an  aliment,  inasmuch  as  it  too  speedily  transforms  into 
excrementitial  bodies,  such  as  urea,  creatinine,  and  sarcosine 
(C8H7N02). 


jo 


Fig.  22. — Creatine. 


Creatine  occurs  as  rhomboidal,  colourless,  and  very  brilliant 
prisms.  It  has  a  sharp,  bitter  taste,  and  dissolves  in  75  parts  of 
cold  water,  in  9410  parts  of  alcohol,  and  not  at  all  in  ether.  The 
solution  has  no  action  on  vegetable  colours,  and  evaporation 
transforms  the  creatine  into  creatinine.    This  transformation 

*   Vide  Beaunis's  'Physiology,'  v^J.  i.,  p.  282. 
t  Methyl-guanidine  acetic  acid. 


NORMAL  ELEMENTS  OF  THE  URINE. 


87 


takes  place  rapidly  in  presence  of  concentrated  acids,  the  r 3 suit 
being  the  loss  of  two  molecules  of  water : 

Creatine.  Creatinine. 
C4H9N302  -  H20  =  C4H7N30. 

With  chloride  of  zinc,  concentrated  solutions  give  a  crystalline 
precipitate  of  chloride  of  zinc  and  creatine.  When  boiled  with 
caustic  alkalies  and  water,  creatine  is  transformed  into  urea  and 
sarcosine,  the  former  being  in  great  part  in  turn  decomposed  into 
carbonate  of  ammonia.  Dilute  mineral  acids  dissolve  creatine 
without  decomposing  it,  and  crystallizable  salts  are  thus 
obtained.    At  the  boiling-point  it  reduces  the  salts  of  mercury. 

Extraction. — A  portion  of  beef  is  minced  and  treated  with 
one  and  a  half  its  volume  of  alcohol  at  90°  C.  ;  it  is  then  heated 
in  a  closed  vessel  on  a  water-bath.  The  same  process  is  re- 
peated, with  a  fresh  portion  of  alcohol.  The  two  alcoholic 
liquids  are  united,  the  fluid  passed  through  linen,  and  the 
alcohol  removed  by  distillation.  The  residue  of  the  distillation 
is  then  diluted  with  water  and  treated  with  an  excess  of  acetate 
of  lead,  and  the  precipitate  which  forms  is  removed  by  nitration 
and  rejected.  The  excess  of  lead  is  removed  by  a  current  of 
sulphuretted  hydrogen ;  and  after  a  second  nitration,  to  separate 
the  sulphide  of  lead,  the  fluid  is  evaporated  in  a  water-bath  to  the 
consistency  of  a  syrup.  After  some  hours'  standing  in  a  cool 
place  crystals  of  creatine  are  deposited.  These  may  be  purified 
by  boiling  in  water  with  animal  charcoal,  filtrated,  and 
crystallized.  Instead  of  minced  beef,  \  Liebig's  Extract  '  may  be 
used,  and  the  subsequent  processes  followed  out  as  above.  The 
quantitative  analysis  of  creatine  is  made  by  weighing. 

By  prolonged  boiling,  creatine  reduces  Fehling's  solution 
without  any  separation  of  cuprous  oxide  ;  and  on  boiling  with  an 
alkaline  mercuric  oxide,  a  transient  red  colour  is  obtained,  and 
ultimately  there  is  a  separation  of  metallic  mercury. 

Creatinine  (C4H7N30).— This  substance,  discovered  by  Liebig 
in  the  urine,  is  a  powerful  non- volatile,  animal  base.  It  dis- 
places ammonia  from  its  salts.  It  forms  prismatic,  colour- 
less, and  very  brilliant  crystals ;  soluble  in  11  parts  of  cold 
water,  100  parts  of  absolute  alcohol,  being  still  more  soluble  in 


THE  URINE  IN  HEALTH  AND  DISEASE. 


these  media  when  heated.  Creatinine  is  but  very  sparingly 
soluble  in  ether.  Its  solutions  are  feebly  alkaline  ;  with  mineral 
acids  it  forms  crystals,  which  are  freely  soluble.  When  concen- 
trated urine  is  treated  with  chloride  of  zinc,  two  double  chlorides 
are  formed — viz.,  a  chloride  of  zinc  and  creatine,  and  a  chloride 
of  zinc  and  creatinine.  Creatinine  exists  in  the  urine  to  the 
extent  of  0*5  to  4*9  grammes  per  diem. 


Fig.  23.— Creatinine. 


The  chloride  of  zinc  and  creatinine — (C4H7NaO),2ZnCL2 — dis- 
solves sparingly  in  cold  water  ;  it  is  more  easily  soluble  in  boiling 
water,  and  is  insoluble  in  alcohol.  The  creatinine  may  be  thus 
isolated.  Nitrate  of  silver,  bichloride,  and  nitrate  of  binoxide 
of  mercury  precipitate  solutions  of  creatinine.  In  alkaline 
solutions  creatinine  is  slowly  transformed  into  creatine  ;  heat 
favours  this  change,  which  spontaneously  takes  place  if  a 
solution  of  creatinine  be  abandoned  for  a  month  or  two. 


Fig.  24.— Double  Chloride  or  Zinc  and  Creatinine. 

Extraction. — In  order  to  extract  creatinine  from  the  urine, 
300  c.c.  of  urine  are  precipitated  with  a  mixture  of  lime-water 
and  of  chloride  of  calcium  ;  if  the  urine  be  albuminous,  the 
albumen  must  be  removed  by  coagulation,  and  if  it  contain 
sugar,  this  must  be  destroyed  by  fermentation.  The  liquid  is  to 
be  concentrated  to  a  syrupy  consistence,  and  from  40  to  50  c.c. 


NORMAL  ELEMENTS  OF  THE  URINE. 


89 


of  alcohol  are  to  be  added  at  a  temperature  of  95°  C.  After 
standing  for  eight  hours,  the  liquid  is  filtered  and  washed  with  a 
little  alcohol.  If  the  solution  occupy  a  volume  of  more  than 
60  c.c,  it  is  to  be  concentrated  in  a  water-bath  ;  on  cooling,  one- 
half  a  c.c.  of  a  saturated  solution  of  chloride  of  zinc  is  to  be 
added,  the  fluid  agitated,  and  allowed  to  stand  for  two  or  three 
days,  at  the  end  of  which  time  creatinine  is  deposited  on  the 
walls  of  the  vessel.  In  order  to  isolate  the  creatinine,  the  double 
salt  is  to  be  dissolved  in  boiling  water,  and  then  boiled  during  a 
quarter  of  an  hour  with  hydrated  oxide  of  lead.  Decolorize  the 
solution  with  animal  charcoal  and  evaporate  to  dryness.  The 
residue  consists  of  a  mixture  of  creatine  and  creatinine. 
Treated  with  alcohol,  the  creatinine  is  dissolved  and  the  creatine 
left  behind.  On  evaporating  the  alcoholic  solution,  the  crea- 
tinine deposits  in  beautiful  crystals  ;  and  the  creatine  may  be 
obtained  by  crystallizing  from  boiling  water,  or  instead  of 
extracting  the  creatinine  from  the  urine,  it  may  be  obtained  by 
the  transformation  of  creatine.  For  this  purpose  the  creatine  is 
to  be  heated  for  about  an  hour  with  hydrochloric  acid  on  a 
water-bath  ;  evaporate  so  as  to  remove  as  much  as  possible  of 
the  free  acid,  when  chlorhydrate  of  creatinine  crystallizes. 
Finally,  these  crystals  are  dissolved  in  about  three  or  four  times 
their  weight  of  water,  and  decomposed  by  boiling  with  oxide  of 
lead ;  chloride  of  lead  is  formed,  and  the  creatinine  is  set  free. 

Tests. — The  presence  of  creatinine  is  demonstrated  by  Weyl's 
test.  Mix  a  few  drops  of  a  dilute  solution  of  nitro-prussiate  of 
soda  and  a  few  drops  of  diluted  caustic  soda  with  the  urine ;  the 
liquid  assumes  a  beautiful  ruby  colour,  which  soon  passes  to 
yellow.  If  after  decoloration  a  little  acetic  acid  be  added,  a 
greenish-blue  colour  is  produced.  The  presence  of  albumen  in 
the  urine  does  not  prevent  this  reaction,  and  it  is  not  caused  by 
any  other  of  the  constituents  of  the  urine.  If  the  urine  be  of 
too  deep  a  colour,  this  reaction  fails.  In  this  case  it  is  necessary 
to  isolate  the  creatinine  in  a  pure  state  by  the  formation  of  a 
chloride  of  zinc  and  creatinine  as  above,  and  then  submit  the 
solution  of  one  or  other  of  these  to  the  action  of  the  nitro- 
prussiate  of  soda  and  the  solution  of  soda.  Creatinine  may  be 
recognised  in  the  urine  by  its  crystalline  form.  Creatinine 


90 


THE  URINE  IN  HEALTH  AND  DISEASE. 


reduces  Fehling's  solution,  and  it  gives  a  yellow  crystalline 
precipitate  when  heated  with  a  dilute  solution  of  phosphomolybdic 
acid,  being  previously  acidified  with  nitric  acid. 

It  renders  red  litmus  blue,  and  nitrate  of  silver  and  bichloride 
of  mercury  precipitate  it. 

Quantitative  Analysis. — The  crystals  of  chloride  of  zinc  and 
creatinine  which  precipitate  as  above  are  collected  on  a  tared 
filter,  washed  with  alcohol,  and  dried  at  100°  C.  Let_p  represent 
the  quantity  of  chloride  of  zinc  and  creatinine  obtained  from  300 
c.c.  of  urine,  then  i9X^~  =  «r,  or  the  amount  of  creatinine  con- 
tamed  in  the  same  volume.  In  order  to  obtain  the  weight  of 
creatinine  per  litre,  divide  the  result  a?  by  3,  and  then  multiply 
by  10. 

Physiology  and  Pathology.— A  healthy  individual  on  a 

mixed  dietary  eliminates,  on  an  average,  1  gramme  of  creatinine 
in  twenty-four  hours,  or,  according  to  Neubauer,  0*60  to  1*20. 
A  highly  nitrogenous  diet  augments  the  proportion.  It  is  also 
augmented  in  acute  febrile  diseases,  as  in  pneumonia,  typhoid 
fever,  intermittent  fever,  tetanus,  etc.    It  diminishes,  on  the 

contrary,  during  convalescence 
from  these  diseases,  and  like- 
wise in  anaemia,  chlorosis, 
muscular  atrophy,  tuberculosis, 
paralysis,  etc. 


Xanthine  and  Hypoxan- 
tiiine. 

Xanthine  (C5H4N4O2)  exists 
but  in  very  small  quantity  in 
normal  urine  (1  gramme  in  800 
litres).  It  is  found  throughout 
the  entire  organism.  Scherer 
has  found  it  in  the  spleen,  the 
pancreas,  and  the  brain.  It  is 
found  in  certain  forms  of 
It  is  increased  in  the  urine  in 


Fig.  25. — Hydrochloratk  and 
Nitrate  of  Xanthine. 

urinary  calculi  of  rare  form, 
leucocytheemia. 


NORMAL  ELEMENTS  OF  THE  URINE. 


91 


It  appears  in  the  form  of  a  white  waxy  body,  sparingly  soluble 
in  water,  and  insoluble  in  alcohol  and  in  ether.  It  is  soluble  in 
ammonia,  potash,  and  caustic  soda.  With  hydrochloric  and 
nitric  acid  it  forms  crystalline  salts.  It  is  precipitated  from  its 
ammoniacal  solution  by  chloride  of  zinc,  chloride  of  calcium, 
and  acetate  of  lead,  and  from  a  hot  aqueous  solution  by  acetate 
of  copper  and  binoxide  of  mercury.  If  xanthine  be  evaporated 
with  nitric  acid,  a  yellow  residue  is  obtained,  which  on  addition 
of  potash  becomes  of  a  yellowish  red  when  cold,  and  of  a  violet 
red  on  being  heated.  When  a  particle  of  xanthine  is  deposited 
on  a  mixture  of  caustic  soda  and  a  little  chloride  of  lime,  it 
encircles  itself  with  a  deep  green  zone,  which  soon  passes  into 
brown  and  disappears. 

Hypoxanthine  (C5H4N40),  or  Sarcine,  is  not  regarded  as  a 
normal  constituent  of  urine.  It  is  a  body  closely  resembling 
xanthine,  and  is  found  in  different  organs  of  the  body,  such  as 
the  liver,  the  spleen,  and  pancreas,  and  sometimes  in  the  urine 
in  cases  of  leucocythaemia.  Hypoxanthine  is  changed  into 
xanthine  by  oxidation.  When  evaporated  with  nitric  acid,  hypo- 
xanthine gives  a  yellow  stain,  which,  on  addition  of  caustic  soda, 
does  not  become  reddish-yellow. 

Oxaluric  Acid. 

Oxaluric  Acid  (C3H4N204). — This  acid  constitutes  one  of  the 
derivatives  of  uric  acid,  and  its  presence  has  been  demonstrated 
in  normal  urine.  According  to  Schunck  and  Neubauer,  it  exists 
in  small  portions  in  the  urine  in  the  condition  of  an  ammoniacal 
salt,  and  exhibits  the  form  of  a  fine  crystalline  powder  of  acid 
taste,  and  very  insoluble  in  water.  Oxalurate  of  ammonia  is, 
on  the  contrary,  very  soluble  in  water.  It  crystallizes  in  the 
form  of  long  prismatic  crystals  united  together  in  tufts  or 
rosettes. 

Allantoine. 

Allantoine  (C4H6N403)  is  a  characteristic  constituent  of  the 
liquor  amnii.  It  is  found  in  the  urine  after  the  internal 
administration  of  uric  acid,  in  fcetal  urine,  and  in  the  urine  of 


92 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


Fig.  26. — Allantotne. 


newborn  children,  in  which  it  may  continue  for  some  days.  It 
crystallizes  in  transparent,  rhomboidal,  colourless  prisms,  which 

are  soluble  in  160  parts  of 
cold  water,  more  soluble  in 
boiling  water  and  alcohol, 
and  insoluble  in  cold  alcohol 
or  ether. 

Succinic  Acid. 
Succinic  Acid  (C4H604) 
has  been  found  in  normal 
urine  by  Meissner  and 
Shepard.  When  benzoic  acid 
is  ingested  its  quantity  is 
augmented.  Succinic  acid 
crystallizes  in  hexagonal 
tables,  which  are  odourless 
and  colourless,  and  remain 
unchanged  in  the  air.  One  hundred  parts  of  water  dissolve 
5*14  grammes  at  a  temperature  of  15°  C,  and  at  a  temperature 
of  100°  C.  100  grammes  of  water  dissolve  120  of  acid.  It  is  not 
very  soluble  in  alcohol,  and  less  so  in  ether.  With  alkalies  it 
forms  soluble  combinations. 

Extraction. — Precipitate  the  urine  with  baryta,  eliminate 

the  baryta  with  an  excess  of 
sulphuric  acid,  and  evaporate. 
Then  acidify  strongly  with  a 
concentrated  solution  of  sul- 
phuric acid,  and  agitate  with 
ether.  Eliminate  the  ether  by 
distillation,  treat  the  residue  with 
water,  heat  to  ebullition,  and 
during  the  process  add  drop  by 
drop  pure  nitric  aeid  until  the 
liquid  presents  a  permanent  yellow  colour.  After  concentration 
of  the  liquid,  succinic  acid  separates  in  a  crystalline  form.  The 
nitric  acid  destroys  all  the  impurities  without  attacking  the 
succinic  acid. 


Fig.  27.— Succinic  Am> 


NORMAL  ELEMENTS  OF  THE  UBINE. 


93 


Tests. — An  aqueous  solution  of  succinic  acid  accurately 
neutralized  by  an  alkali  gives,  with  perchloride  of  iron,  a  reddish 
precipitate,  which  is  insoluble  in  mineral  acids.  A  fragment  of 
succinic  acid  heated  in  a  test-tube  evolves  white  vapours  of  a 
nature  irritating  to  the  tracheal  mucous  membrane.  The 
solution,  or  that  of  its  combination  with  potash  or  soda,  gives  a 
white  precipitate  with  alcohol. 

Benzoic  Acid. 

Benzoic  Acid  (HC7H502)  is  not  a  normal  constituent  of  urine, 
but  is  found  in  it  during  putrefaction,  being  derived  from 
hippuric  acid.  It  is  found  in 
the  urine  after  the  ingestion  of 
benzoic  acid,  or  of  substances 
which  are  transformed  in  the 
organism  into  this  acid,  such 
as  cinnamon,  benzoin  balsam, 
balsam  of  tolu,  quinine,  prunes, 
etc.  Benzoic  acid  crystallizes 
in  the  form  of  fine  colourless 
needles  or  brilliant  scales.  It 
sublimes  at  240°  C.  without  de- 
composition, and  is  very  soluble 
in  ether.  It  is  difficult  of  solution  in  cold  water,  but  dissolves 
more  readily  in  boiling  water.  Alcohol,  ether,  acetic  acid,  and 
petroleum-ether  dissolve  it  readily.  Its  solutions  redden  litmus, 
and  with  alkalies  it  forms  salts  soluble  in  water  and  in  alcohol. 

Extraction. — In  order  to  extract  it  from  the  urine,  the  liquid 
is  concentrated  to  the  consistence  of  an  extract,  and  then 
treated  with  alcohol.  The  alcohol  is  removed  by  evaporation, 
and  the  aqueous  residue  is  treated  with  hydrochloric  acid,  where- 
upon the  benzoic  acid  separates. 

Oxalic  Acid. 

Oxalic  Acid  — Oxalate  of  Lime  (C2H204+2H20).— The 
most  important  of  the  non -nitrogenous  organic  acids  of  the  urine 
is  oxalic  acid.  It  is  frequently  found  in  the  urine,  but  only  in 
small  quantity,  amounting  to  about  2  grammes  in  twenty -four 


Fjg.  28. — Benzoic  Acid. 


94 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


hours.  It  is  found  under  the  form  of  oxalate  of  lime,  in  which 
combination  it  forms  the  greater  part  of  the  '  mulberry  calculus.' 
It  crystallizes  in  rhomboidal  colourless  crystals,  soluble  in  water 
and  in  alcohol. 

Oxalate  of  lime  forms  small  square,  brilliant,  octahedral 
crystals,  which  are  perfectly  transparent,  strongly  refract  light, 
and  present  the  appearance  of  an  ordinary  letter  envelope.  At 
other  times  it  presents  a  lozenge  form,  or  that  of  a  triangle  with 
terminal  pyramids,  and  is  not  unfrequently  found  in  the  '  dumb- 
bell '  form.    Oxalate  of  lime  is  insoluble  in  water,  sparingly 


soluble  in  acetic  acid,  but  is  easily  soluble  in  hydrochloric  and 
nitric  acid.  It  also  dissolves  in  acid  phosphate  of  soda,  which 
accounts  for  its  being  found  in  solution  in  the  urine. 

Detection  and  Isolation  from  Urine.— Mix  from  400  to 
<yQ0  c.c.  of  urine  with  ;i  solution  of  chloride  of  sodium,  saturate 
with  ammonia,  and  redissolve  with  acetic  acid  the  precipitate 
which  forms,  avoiding  an  excess  of  the  acid.  At  the  end  of 
twenty-four  hours  a  new  precipitate  forms,  in  which  oxalate  of 
lime  is  found  with  uric  acid.  The  precipitate  is  gathered  on  a 
filter,  washed  with  water,  and  treated  with  a,  few  drops  of  hot 
hydrochloric  acid,  which  dissolves  the  oxalate  of  lime,  leaving 
the  uric  acid.  The  filtered  Liquid  is  then  collected  in  a,  test-tube, 
diluted  with  15  c.c.  of  water,  and  very  dilute  ammonia  added 
•<lrop  by  drop.    After  an  interval  of  some  hours,  oxalate  of  lime 


Fig.  29. — Oxalate  of  Lime. 


NOBMAL  ELEMENTS  OF  THE  URINE. 


95 


is  deposited,  which  may  be  recognised  on  microscopic  examina- 
tion by  its  characteristic  appearance. 

Quantitative  Analysis. — The  crystals  are  collected  on  a 
small  filter,  washed  with  warm  water,  and  dried.  Having 
detached  them  from  the  filter,  the  latter  is  incinerated  in  a  tared 
platinum  capsule ;  then  the  crystals  are  added  and  calcined  at 
a  faint  red  heat.  When  thus  treated,  the  oxalate  of  lime  is 
transformed  into  carbonate  of  lime.  In  order  to  change  into 
carbonate  the  portion  which  may  have  been  transformed  into 
caustic  lime,  the  cold  residue  is  saturated  with  carbonate  of 
ammonia,  slowly  evaporated  to  dryness,  and  ignited  as  above  ; 
this  process  being  repeated  till  the  weight  no  longer  increases. 
There  but  remains  to  weigh  the  residual  carbonate  of  lime,  of 
which  100  parts  correspond  to  135  crystallized  oxalate  of 
lime. 

Physiology  and  Pathology. — The  presence  of  oxalate  of  lime 
in  urine  may  be  due  to  mere  disturbances  of  digestion.  It  may 
be  derived  from  the  ingestion  of  certain  aliments,  such  as 
rhubarb,  sorrel,  tomatoes,  chicory,  ginger,  etc.,  and  as  the  result 
of  poisoning  by  salt  of  soirel  (binoxalate  of  potash).  In  cases  of 
physiological  oxaluria,  the  urine  deposits  crystals  of  oxalate  of 
lime,  even  when  it  contains  but  minute  proportions,  the  acidity 
of  the  urine  being  insufficient  to  maintain  in  solution  all  the 
oxalate  eliminated  by  the  kidney.  Oxalic  acid  results  from  the 
oxidation  of  the  hydrocarbons,  the  albuminoids,  and  the  fatty 
and  saccharine  constituents  of  the  body.  Oxalate  of  lime  fre- 
quently occurs  in  the  urine  in  cases  of  nervous  affections,  and 
especially  where  there  is  embarrassment  of  the  respiration  from 
this  cause.  In  cases  of  diabetes  there  is  an  augmented  ex- 
cretion of  oxalic  acid,  and  sometimes,  when  the  sugar  diminishes, 
it  does  so  in  greater  proportion  than  oxalic  acid,  and  vice  versa. 

As  constituting  an  essential  disease,  as  described  by  Begbie, 
oxalate  of  lime  may  continue  for  a  long  time  in  the  urine,  and 
cause  the  state  known  as  the  oxalic  acid  diathesis.  In  cases  of 
spermatorrhoea,  in  common  with  other  observers,  I  have  fre- 
quently found  oxalate  of  lime  in  the  urine.  Chronic  prostatitis 
may  in  these  cases,  to  some  extent,  account  for  its  formation. 


96 


THE  URINE  IN  HEALTH  AND  DISEASE 


VOLATILE  ACIDS  (PHENOLS). 

Under  the  volatile  acids,  or  phenols,  are  comprised  bodies 
containing  at  least  six  atoms  of  carbon.  Several  of  these  con- 
stituents exist  in  the  urine.  The  phenols  properly  so  called — 
viz.,  phenic  or  carbolic  acid,  paracresol,  and  pyrocatechin — 
are  found  in  the  urine  with  potash. 

Phenic  Acid  (C6H5OH)  is  found  with  indol  and  skatol 
during  putrefactive  decomposition  of  proteids.  Its  homologue 
paracresol  (C(;H4OH,CH8)  is  not  found  free  in  urine,  but  exists 
as  cresysulphuric  acid  (C7H70,S02OH).  The  amount  of  phenic 
acid  in  urine  notably  augments  when  this  agent  is  used  either  by 
external  application  or  internal  administration.  When  present 
in  the  urine,  the  fluid  presents  a  greenish-brown  colour,  which 
on  contact  with  air  changes  into  a  dark  brown.  This  is  due  to 
the  formation  of  hydroquinone,  the  consequence  of  the  absorption 
of  oxygen  by  the  phenic  acid. 

Detection  in  Urine. — In  order  to  isolate  phenic  acid  from 
urine,  treat  200  c.c.  of  the  fluid  with  40  c.c.  of  hydrochloric  acid, 
and  distil  to  about  150  c.c.  Filter  a  little  of  the  fluid,  and  add 
a  little  bromine  water,  when,  if  the  urine  contain  phenic  acid, 
a  flocculent  yellowish-white  precipitate  is  obtained,  which  is 
more  or  less  crystalline,  and  evolves  the  odour  of  phenic  acid. 
Perchloride  of  iron  causes  a  violet  colour,  and  Millon's  reagent 
hot,  a  red  colour.  A  mixture  of  aniline  and  hypochlorite  of 
sodium  gives  a  blue  colour,  which  passes  into  red,  and  which 
alkalies  restore  to  blue. 

Hydroquinone  (C(.(H4(OH)2)  —  Paradioxybenzol  —  is  not  a 
normal  constituent  of  urine,  but  results  from  the  ingestion  of 
phenic  acid  and  benzol.  As  found  in  the  urine,  it  is  an  ethereal 
compound  with  sulphuric  acid.  The  dark  colour  which  urine 
containing  phenic  acid  assumes  on  exposure  to  air  is  due  to  it.  In 
common  with  pyrocatechin,  it  reduces  metallic  salts,  but  unlike 
it,  it  is  nearly  insoluble  in  cold  benzol,  and  the  two  may  be  thus 
separated. 

Pyrocatechin,  or  Alkaptonc  (CGH402),  occurs  in  the  urine 
after  the  ingestion  of  phenic  acid  and  benzol.    Urine  which 


NOEMAL  ELEMENTS  OF  THE  URINE. 


97 


contains  pyrocatechin,  left  in  contact  with  air,  assumes  a  dark- 
brown  colour,  owing  to  the  formation  of  hydro quinone,  as  obtains 
in  the  case  of  phenic  acid.  The  same  change  occurs  after  the 
administration  of  naphthaline,  aniline,  salicylic  acid,  and 
arbutine.  A  dilute  solution  of  ferric  chloride  turns  solutions  of 
pyrocatechine  into  an  emerald -green  colour.  If  this  solution  be 
then  acidulated  with  tartaric  acid,  it  becomes  violet  on  addition 
of  ammonia,  and  purplish-red  on  the  addition  of  an  excess  ;  the 
green  colour  may  again  be  restored  by  an  excess  of  acetic  acid. 
It  is  distinguished  from  hydroquinone  by  yielding  a  precipitate 
with  normal  acetate  of  lead,  which  is  soluble  in  acetic  acid.  The 
occurrence  of  this  substance  in  the  urine  of  herbivora  is  probably 
due  to  certain  constituents  of  their  food. 

Indol  (C8H7N)  occurs  in  the  faeces  with  sJcatol,  occasioning  the 
characteristic  odour.  It  arises  from  the  putrefactive  decom- 
position of  proteids.  Skatol  (C9H9N)  has  a  similar  origin.  It  is 
found  in  the  urine  in  the  form  of  skatoxy sulphate  of  potash. 
When  urine  contains  skatol,  the  addition  of  hydrochloric  acid 
and  chloride  of  lime  causes  a  violet  tint,  which  is  unaffected 
by  ether  and  chloroform.  Robin  regards  skatol  as  a  normal 
constituent  of  urine,  and  as  being  allied  to  urobiline  uro- 
erythrine. 

Colouring  Matters. 

It  is  still  doubtful  to  which  pigment  the  colour  of  the  urine  is 
due.  In  all  probability  it  is  due  to  more  than  one,  which  result 
from  the  oxidation  of  the  chromogenous  principles. 

Urobiline  (C^H^N^). — This  principle  was  discovered  by 
Jaffe  and  obtained  by  Maly,  who  named  it  '  hydrobilirubine,'  by 
the  action  of  an  amalgam  of  sodium  on  bilirubine.  Urobiline 
exists,  but  rarely  fully  formed,  in  normal  urine  at  the  period  of 
emission.  It  is,  however,  produced  when  a  mineral  acid  is 
added  to  urine  and  the  fluid  exposed  to  air.  The  urine  is  thus 
supposed  to  contain  a  chromogenous  principle,  which  gives 
origin  to  it.  It  is  usually  believed  to  be  derived  from  bilirubine 
and  biliverdine  by  a  process  of  reduction  in  the  intestines. 
According  to  Hayem,*  the  bile  may  contain  urobiline,  and  it 
*  Le  Progres  3/tdicalt  August  6,  1887. 

7 


98 


THE  UKINE  IN  HEALTH  AND  DISEASE 


may  be  produced  as  a  pigment  by  this  organ  when  it  is  torpid  or 
in  a  diseased  condition. 

Properties  of  Urobiline. — Normal  urobiline  is  an  oxidation 
product  of  effete  haematin  and  bile  pigments.  It  is  an  amorphous 
substance  of  a  brownish-red  colour,  very  sparingly  soluble  in 
water,  but  easily  soluble  in  alcohol  and  chloroform,  and  less 
easily  in  ether.  Its  solutions  when  concentrated  are  of  a  dark- 
brown  colour,  passing  to  reddish-yellow,  and  to  rose  colour  by 
dilution.  Neutral  solutions  of  urobiline  present  a  beautiful 
fluorescent  green,  which  is  destroyed  by  an  acid,  but  restored  by 
neutralization  by  an  alkali.  On  spectroscopic  examination  a 
black  band  is  found  to  exist  between  the  green  and  the  blue. 

Reaction. — Urine  containing  urobiline  presents  a  rose  or 
yellowish-rose  colour,  according  to  the  amount  of  the  colouring 
matter  present ;  on  the  addition  of  ammonia  the  tint  becomes 
clearer,  passing  to  green.  Nitric  acid  causes  a  reddish-brown 
colour,  which  passes  to  a  violet-red  or  blue  on  addition  of  hydro- 
chloric or  sulphuric  acid.  If  100  c.c.  of  urine  be  agitated  with 
half  its  volume  of  ether,  and  if  the  latter  be  evaporated,  a 
residue  is  obtained,  which,  on  the  addition  of  a  little  absolute 
alcohol  gives  a  rose  coloration  and  an  intense  green  fluor- 
escence. 

Pathology. — Urobiline  exists  in  augmented  amount  in  the 
urine  in  all  febrile  affections,  such  as  acute  gout,  pneumonia, 
pleurisy,  rheumatism,  gastric  derangements,  and  as  the  result  of 
various  internal  haemorrhages.  It  is  especially  augmented  in 
certain  diseases  of  the  liver,  such  as  cirrhosis,  and  all  patho- 
logical states  which  occasion  an  exaggerated  destruction  of  the 
red  globules  of  the  blood.  Urobilinuria  appears  to  be  linked 
with  an  alteration  of  the  liver  cells ;  in  this  case  the  bile  is 
decolorized,  and  contains  a  marked  quantity  of  urobiline.  This 
alone  will  not  cause  jaundice.  In  the  hcemapheic  jaundice  of 
Gubler,  other  colouring  matters  than  urobiline  exist  in  the  urine, 
arising  from  intra-organic  modifications  of  bilirubine  and  bili- 
verdine.  MacMunn  has  described  two  bodies  allied  to  uro- 
biline—  viz.,  febrile  urobiline  and  urohcematojporphyrine. 
The  latter  pigment  can  be  separated  from  urine  in  the  Bame 
manner  as  urobiline.    It  has  been  found  in  Addison's  disease, 


NOEMAL  ELEMENTS  OF  THE  URINE. 


99 


acute  rheumatism,  cirrhosis  of  the  liver,  croupous  pneumonia, 
pericarditis,  Hodgkin's  disease,  etc. 

Urochrome  and  Uroerythrine  (ovpov,  urine,  and  spvOpog,  red). 
— Thudichum  considers  that  the  urine  contains  but  one  pigment, 
which  he  has  named  urochrome.  It  is  a  product  much  less  defined 
than  urobiline,  with  which  Maly,  indeed,  considers  it  identical.* 
It  is  a  yellow  substance,  which  dissolves  with  difficulty  in  alcohol, 
but  easily  in  ether.  On  becoming  oxidized  in  contact  with  air, 
urochrome  becomes  converted  into  a  red  body,  to  which  Heller 
has  given  the  name  uroerythrine.  This  constitutes  the  colouring 
matter  of  the  pink  urates.  It  is  found  also  with  urobiline  in  the 
red  deposits  of  uric  acid.  The  deep  reddish-yellow  colour  of  the 
urine  of  acute  rheumatism,  affections  of  the  liver,  etc.,  is  due  to 
products  of  uroerythrine.  It  is  'stated  that  the  red  principle  of 
uroerythrine  submitted  to  the  influence  of  oxidizing  agents  is 
transformed  into  three  substances  :  A  dark  powder,  uromelanine 
(/LisXag,  black — C36H43N7O10),  which  is  soluble  in  potash,  and 
appears  to  perform  the  role  of  an  acid.  The  alcoholic  solution, 
which  is  coloured  ruby-reel,  gives  on  the  addition  of  water  a 
precipitate  of  a  resinous  aspect,  which  is  separable  by  ether  into 
two  parts,  the  one  insoluble  in  that  liquid,  uropittine  {Trirra, 
pitch — C9H10N2O3),  which  is  soluble  in  alcohol,  and  the  other, 
omicholic  acid,  insoluble  in  ether. 

Indican  (C8H6NS04K). —  Indican,  or  the  uroxanthine  of 
Heller,  is  always  found  in  normal  urine,  but  only  to  the  extent 
of  from  5  to  20  milligrammes  in  twenty-four  hours.  Its  propor- 
tion is  notably  augmented  in  cases  of  intestinal  obstruction, 
diffuse  peritonitis,  cholera,  cancer  of  the  liver  and  stomach,  and 
pernicious  anaemia. 

Under  the  influence  of  oxidizing  agents,  indican  is  transformed 
into  two  other  pigments — the  one  blue,  uroglaucine  or  indigo- 
tine,  the  other  red,  urrhodine  or  indirubine.  The  same 
doubling  takes  place  when  urine  containing  indican  enters  into 
putrefaction  ;  and  if  the  chromogen  is  in  notable  quantity, 
agitation  in  air  causes  the  urine  to  become  of  a  violet-blue 
colour.  In  rare  cases  the  transformation  of  indican  takes  place 
in  the  urinary  passages,  when  the  urine  is  emitted  of  a  blue 
*  Liebig's  Ann.,  Bd.  clxviii.  (1872),  S.  90. 


100 


THE  URINE   IN  HEALTH  AND  DISEASE. 


colour.  Uroglaucine  and  urrhodine  have  also  been  found  in 
sediments  and  urinary  calculi. 

Tests. — Boil  urine  with  a  tenth  of  its  volume  of  hydrochloric 
acid,  or  treat  it  cold  with  two  or  three  times  its  volume  of  the 
same  acid,  when,  if  it  contains  indican,  a  violet  coloration 
ensues.  As  a  control  test,  agitate  the  same  urine  with  ether, 
which  will  take  up  the  urrhodine  produced  at  the  same 
time.  Urine  containing  albumen  is  also  coloured  violet  by 
hydrochloric  acid  ;  but  the  albumen  may  be  removed  by  coagula- 
tion, and  recognised  by  its  own  special  tests.  M.  Obermayer0 
recommends  that  the  urine  be  treated  with  a  solution  of  acetate 
of  lead,  avoiding  an  excess,  aud  filtered ;  the  nitrate  is  now 
agitated  with  an  equal  volume  of  hydrochloric  acid,  containing 
from  2  to  4  per  cent,  of  perchloride  of  iron  ;  a  little  chloroform 
is  then  added,  which  gives  a  transparent  liquid  of  a  pure  blue 
colour. 

Uroglaucine  (Indigo  blue— C1()H10N2O2-f-2H2O).  —  This  prin- 
ciple, by  its  composition  and  properties,  resembles  vegetable 
indigo,  in  appearing  as  an  amorphous  powder  composed  of 
microscopic  crystals.  It  is  insoluble  in  water,  sparingly  soluble 
in  concentrated  alcohol  and  boiling  ether  ;  it  is  more  soluble  in 
cold  chloroform.  In  order  to  separate  uroglaucine  from  the 
urine,  the  fluid  is  filtered,  the  blue  matter  remaining  on  the  filter 
is  treated  with  concentrated  boiling  alcohol;  a  violet  solution 
is  thus  obtained.  This  is  evaporated,  the  residue  washed  with 
cold  water,  and  redissolved  in  boiling  alcohol.  On  carefully 
evaporating,  blue  prismatic  crystals  of  uroglaucine  are  deposited. 
In  order  to  extract  uroglaucine  from  sediments,  the  sediment  is 
washed  on  a  filter,  at  first  with  hydrochloric  acid,  then  with 
water,  and  the  dried  filter  is  exhausted  with  chloroform. 

Urrhodine,  or  indirubine  (indigo  red),  is  a  b.own  amorphous 
substance,  insoluble  in  water,  but  soluble  in  alcohol,  ether,  and 
chloroform.  Its  solutions  are  of  a  red  colour.  In  order  to 
separate  urrhodine  from  the  urine,  it  is  acidified  with  a  little 
hydrochloric  or  acetic  acid,  filtered, and  agitated  with  chloroform 
or  ether.    The  solvent  is  then  evaporated,  and  the  urrhodine 

*  Chemi*.  Centralblatt,  1890,  p.  273,  and  Pharm.  Zeits,  fur  Russ., 
xxix.,  1S(J0,  504. 


NORMAL  ELEMENTS  OF  THE  URINE. 


101 


remains.  This  pigment  is  easily  removed  with  cold  alcohol  or 
ether. 

PATHOLOGICAL  SIGNIFICANCE  OF  URINE, 

As  from  Colour  and  Density. 

Pale  urine  emitted  in  average  quantity  and  of  feeble  density 
indicates,  in  the  first  place,  that  there  is  no  acute  febrile 
affection.  Pale  urine,  abundantly  secreted,  of  a  low  specific 
gravity,  points  to  cirrhosis  of  the  kidney,  with  desquamation  of 
renal  epithelium,  and  unfavourable  prognosis.  Here  uraemia 
threatens.  In  anaemia  the  urine  is  pale  and  of  low  specific 
gravity ;  chloro-anaemia  is  revealed,  not  only  by  the  pallor 
of  the  mucous  membranes,  but  by  the  decoloration  of  the 
urine.  In  this  case  there  is  a  deficiency  of  red  globules,  and 
consequently  of  haemoglobin,  whereby  oxidation  is  diminished, 
and  hence  the  normal  colouring  matters  of  the  urine  thus 
formed  are  in  lessened  quantity.  Thudichum  therefore  properly 
regards  the  absence  of  urochrome  in  the  urine,  and  its  retention 
in  the  organism,  or  rather,  perhaps,  its  non-formation,  as  one 
of  the  characteristics  of  anaemia.  Urochrome  retained  in  the 
system  oxidizes  gradually,  giving  origin  to  omicholic  acid  and 
uropittine,  which  are  found  in  the  tissues,  and  in  the  tartar  of 
the  teeth,  and  are  thus  a  cause  of  fcetidity  of  breath. 

In  hysteria  large  quantities  of  pale  urine  are  secreted,  as  after 
the  ingestion  of  large  draughts  of  water,  or  the  use  of  diuretics 
and  alcohol. 

When  the  urine  is  strongly  coloured  yellow,  it  is  usually  found 
to  contain  indican,  as  in  cases  of  cholera.  It  is  of  a  like  colour 
after  the  ingestion  of  substances  containing  crysophanic  acid,  as 
santonine,  rhubarb,  senna,  etc.  These  urines  become  red  on  the 
addition  of  an  alkali. 

Red  Urines  are  usually  of  a  high  density,  and  are  rich  in 
solid  principles.  Such  is  the  urine  secreted  during  night,  and 
the  urine  of  febrile  affections  generally.  Sediments  of  urate  of 
soda  are  usually  whitish,  but  other  urates  are  of  a  brick  colour, 
or  almost  red,  from  containing  a  large  amount  of  colouring 
matter.    When  the  urine  undergoes  putrefaction,  indican  is 


102 


THE  URINE  IN  HEALTH  AND  DISEASE. 


transformed  into  uroglaucine  and  indirubine  (urrhodine). 
Uroglaucine  and  urrhodine  rarely  form  in  the  bladder.  They 
are  sometimes  found  in  cases  of  Bright's  disease  and  in  catarrh 
of  the  bladder,  when  the  urine  has  become  ammoniacal.  The 
two  substances  may  be  separated  by  ether. 

Brown  Urines  usually  contain  abnormal  colouring  matters, 
such  as  those  of  the  bile  and  blood.  In  cases  of  melanotic 
cancer  the  urine  is  black,  from  the  presence  of  melanin.  Where 
iodine  and  bromine  have  been  taken  to  a  considerable  extent, 
the  addition  of  nitric  acid  to  the  urine  causes  the  appearance 
of  a  brown  colour  from  the  liberation  of  the  iodine  and  bromine. 

TO  ESTIMATE  THE  TOTAL  NITROGEN  OF  THE 
URINE. 

The  following  is  Kjaldahl's  Method,  modified  by  Pfltiger  and 
Bohland  :  Take  5  c.c.  of  urine  of  average  concentration,  and 
place  in  an  Erlenmeyer's  flask  holding  300  c.c,  together  with 
20  c.c.  of  concentrated  sulphuric  acid ;  boil  the  mixture  on  wire- 
gauze,  over  a  large  Bunsen  flame,  until  all  water  and  gases  formed 
are  driven  off.  The  fluid  at  first  becomes  black,  but  afterwards 
of  a  yellow  tint,  when  the  heat  should  be  diminished.  From 
twenty-five  or  thirty  minutes  are  required  for  the  heating.  The 
fluid  is  then  allowed  to  cool,  diluted  with  water  to  200  c.c,  and 
placed  in  a  flask  ;  80  c.c  of  caustic  soda  solution,  cf  a  specific 
gravity  of  1*3,  are  then  added,  the  llask  speedily  corked,  and  its 
contents  distilled  into  a  measured  quantity  of  standardized 
sulphuric  acid. 

The  nitrogen  of  the  urine  is  converted  by  this  process  into 
ammonia.  The  ammonia  combines  with  the  sulphuric  acid,  and 
the  quantity  of  ammonia  formed  is  at  once  known  if  we  know  the 
amount  of  sulphuric  acid  which  lias  been  neutralized.  The 
excess  of  sulphuric  acid  is  determined  by  til  rat  ion  with  standard 
caustic  soda,  and  this  excess  deducted  from  the  quantity  of 
sulphuric  acid  originally  taken  gives  the  amount  which  has  been 
neutralized.  The  ammonia  thus  determined  is  easily  calculated 
to  nitrogen,  17  parts  of  ammonia  containing  14  parts  of  the 
latter. 


CHAPTER  III. 


NORMAL  ELEMENTS  OF  THE  URINE. 

Inorganic  Substances. 

Chloride  of  Sodium. 

Chloride  of  Sodium — Qualitative  and  Quantitative  Analysis — Patho- 
logical Significance  — Sulphuric  Acid  and  Sulphates— Analysis — 
Quantitative  Analysis  of  Sulphuric  Acid  and  of  Sulphur — Patho- 
logical Significance — Phosphoric  Acid  and  Phosphates — Phospho- 
glyceric  Acid — Qualitative  and  Quantitative  Analysis  of  Phosphoric 
Acid — Variations  of  Phosphoric  Acid  in  Urine— Potash  Soda — Lime 
— Magnesia — Qualitative  Analysis — Ammonia — Iron — Nitric  Acid 
and  Nitrates  and  Nitrites — Silica — Peroxide  of  Hydrogen — Gases  in 
Urine. 

Next  to  urea,  chloride  of  sodium  is  the  most  abundant  element 
of  the  urine,  of  which  it  forms  almost  two- thirds  of  the  mineral 
substances.  The  chlorides  of  potassium,  of  calcium,  and  of 
magnesium  exist  only  in  feeble  proportions  in  urine. 

In  the  normal  condition  the  amount  of  chloride  of  sodium 
eliminated  by  the  urine  in  twenty-four  hours  is  from  10  to  13 
grammes.  Corresponding  to  the  quantity  of  food  ingested,  it 
necessarily  varies. 

Chloride  of  sodium  is  a  colourless,  inodorous  salt,  of  great 
solubility  in  water,  and  little  soluble  in  alcohol.  When  a  solution 
of  chloride  of  sodium  is  evaporated  on  a  glass  slide,  it  separates 
from  solution  in  the  form  of  cubic  crystals  ;  from  evaporated 
urine  it  deposits  as  octahedral  and  tetrahedral  crystals.  Solu- 
tions of  chloride  of  sodium,  in  common  with  chlorides  of 
potassium,  calcium,  and  magnesium,  give  a  white  precipitate 


104 


THE  UBINE  IN  HEALTH  AND  DISEASE. 


with  nitrate  of  silver,  insoluble  in  nitric  acid,  but  easily  soluble 
in  ammonia,  and  which  blackens  on  exposure  to  light. 

Qualitative  Analysis.  —  On  microscopic  examination,  the 
characteristic  octahedral  crystals  are  recognised.  These  crystals 
communicate  to  the  flame  of  alcohol  a  yellow  colour.  Add  to 
urine  so  as  to  render  it  strongly  acid  a  few  drops  of  nitric  acid, 
and  then  a  few  drops  of  a  solution  of  nitrate  of  silver.  A  white, 
dense  precipitate  of  chloride  of  silver  is  formed.  Nitric  acid  is 
added  in  this  case  to  prevent  the  precipitation  of  other  salts  of 
silver,  especially  the  phosphate. 

Quantitative  Analysis. — This  is  accomplished  by  means  of 
a  titrated  solution  of  nitrate  of  silver,  which  contains  29*062 
grammes  per  litre. 

The  process  of  Mohr  is  based  upon  the  fact  that  by  the 
addition  of  nitrate  of  silver  to  urine  containing  neutral  chromate 
of  potash  all  the  silver  is  precipitated,  in  the  first  place,  in 
the  form  of  chloride  of  silver,  and  ultimately  of  chromate  of 
silver,  the  latter  appearing  as  a  red  precipitate.  By  means  of  a 
graduated  pipette  pour  into  a  glass  jar  10  c.c.  of  urine,  to  which 
add  0*5  c.c.  of  a  concentrated  solution  of  neutral  chromate  of 
potash.  Introduce  the  standard  solution  of  nitrate  of  silver,  of 
which  each  c.c.  precipitates  0*010  gramme  of  chloride  of  sodium 
by  means  of  a  graduated  burette.  Add  drop  by  drop,  constantly 
agitating  until  the  red  coloration  which  is  produced  at  the  lines 
of  contact  of  the  two  fluids  does  not  disappear.  The  first  trace  of 
the  red  colour  indicates  the  end  of  the  reaction.  Note  the 
quantity  of  the  nitrate  of  silver  solution  employed,  when  the 
amount  of  chloride  is  easily  calculated.  Owing  to  various  cir- 
cumstances, this  method  is  not  absolutely  accurate,  and  in  order 
to  ensure  greater  accuracy,  all  the  organic  matter  should  be 
decomposed  by  nitric  acid. 

To  the  clinician,  an  approximation  of  the  quantity  of  chloride 
of  sodium  is  usually  sufficient.  To  ascertain  this,  add  to  urine 
previously  acidified  by  nitric  acid  a  strong  solution  of  nitrate  of 
silver  (8  per  cent,  or  thereby).  If  the  quantity  of  the  chloride  is 
normal,  a  compact  whitish-gray,  caseous  precipitate  is  formed, 
which  deposits  readily,  and  separates  on  agitation  in  whitish 
flakes.    Ultimately  these  flakes  deposit,  and  leave  a  clear  super- 


NORMAL  ELEMENTS  OF  THE  URINE. 


105 


natant  fluid.  The  smaller  the  quantity  of  the  chloride  of 
sodium,  the  less  dense  is  the  precipitate.  When  the  quantity  is 
very  small,  a  milky  colour  alone  is  produced. 

The  following  modification  of  the  silver  process  has  been  sug- 
gested by  Freund  and  Topfer  (Centralb.  f.  Klin.  Medic,  1892, 
N.  38,  p.  801).  To  urine  is  to  be  added  a  solution  containing 
3  per  cent,  of  acetic  acid  and  10  per  cent,  of  acid  acetate  of  soda, 
by  which  the  precipitation  of  uric  acid,  xanthine,  and  colouring 
matters  is  prevented  in  the  form  of  precipitate  with  acid  nitrate 
of  silver.  To  5  or  10  c.c.  of  urine  add  15  or  20  c.c.  of  water. 
To  the  urine  thus  diluted  add  25  c.c.  of  the  acetic  solution,  a  few 
drops  of  a  10  per  cent,  solution  of  bichromate  of  potash,  and 
finally  the  nitrate  of  silver  solution,  prepared  after  Mohr's 
method. 

Pathological  Significance.  —  (1)  In  all  febrile  affections 
(especially  in  pneumonia)  there  is  a  diminution  of  the  chloride  of 
sodium  in  the  urine.  According  to  Yogel,  in  intermittent  fever 
the  elimination  of  chloride  of  sodium  is  more  considerable  in  the 
febrile  stage  than  during  the  apyretic  intervals.  The  complete 
disappearance  of  chloride  of  sodium  in  febrile  affections  is  of 
grave  import,  its  reappearance  being  of  favourable  significance. 

(2)  In  chronic  affections  the  quantity  of  chloride  of  sodium 
and  of  urea  is  proportionate  to  the  general  nutrition. 

(3)  In  renal  affections,  with  albuminuria  or  anasarca,  there 
is  augmentation  of  the  chlorides  when  previous  retention  of  these 
salts  occurred.  When  absorption  of  the  exudations  which  contain 
a  large  proportion  of  chloride  of  sodium  takes  place,  the  chloride 
of  sodium  in  the  urine  may  amount  to  almost  55  grammes  in 
twenty-four  hours. 

Sulphuric  Acid  and  Sulphates. 

Sulphuric  acid  is  found  in  the  urine  in  two  forms  — viz., 
in  combination  with  sodium  and  potassium  as  sulphates,  and 
in  combination  with  phenols.  In  the  normal  condition  the 
quantity  of  sulphuric  acid  united  with  the  latter  forms  but 
the  tenth  part  of  the  total  sulphuric  acid.  Almost  all  the 
normal  sulphuric  acid  of  the  urine  is  combined  with  potash  and 
soda  in  nearly  equal  proportions,  and  hence  in  analysis  the 


106 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


proportion  of  acid  alone  is  indicated,  the  base  with  which  it  is 
combined  not  being  considered. 

Analysis. — The  presence  of  sulphuric  acid  is  demonstrated  in 
the  following  manner :  Strongly  acidify  the  urine  with  acetic 
acid,  and  add  a  solution  of  chloride  of  barium.  A  fine  granular, 
white  precipitate  of  sulphate  of  barium,  insoluble  in  hydro- 
chloric, nitric,  and  acetic  acids,  results.  When  the  sulphuric 
acid  is  combined  with  the  phenols,  mix  urine  strongly  acidified 
by  acetic  acid  with  an  excess  of  chloride  of  barium,  and  filter. 
Add  hydrochloric  acid  to  the  filtrate,  when  a  second  precipitate 
of  sulphate  of  barium  is  formed.  Sulphur  exists  in  the  urine  in 
infinitesimal  quantity  independently  of  that  contained  in  the 
sulphuric  acid.  To  detect  this,  add  to  urine  hydrochloric  acid, 
so  as  to  render  it  strongly  acid,  and  remove  all  the  sulphuric  acid 
by  digestion  with  chloride  of  barium,  and  treat  the  liquid  with 
pure  carbonate  of  soda,  filter,  add  a  little  saltpetre  to  the  filtrate, 
and  evaporate.  Ignite  the  residue,  add  pure  hydrochloric  acid, 
and  evaporate  several  times  to  dryness  with  hydrochloric  acid 
until  all  the  nitric  acid  is  expelled.  Finally,  dissolve  the  residue 
in  water.  The  solution  will  contain  the  sulphur  in  the  form 
of  sulphuric  acid,  and  give  a  precipitate  with  hydrochloric  acid 
and  chloride  of  barium. 

Quantitative  Analysis  of  Sulphuric  Acid.— Into  a  conical 
glass  vessel  pour,  with  two  or  three  volumes  of  water,  25  to 
50  c.c.  of  filtered  urine.  Acidify  strongly  with  hydrochloric 
acid,  heat  almost  to  boiling,  and  precipitate  with  an  excess  of 
chloride  of  barium,  and  expose  to  moderate  heat.  When  the 
liquid  has  become  clear,  separate  the  supernatant  fluid  from  the 
precipitate.  Wash  the  latter  with  boiling  water,  decant  anew 
on  the  filter,  and  continue  the  operation  until  the  water  of  the 
washing  is  no  longer  acid.  Finally,  place  the  precipitate  on  a 
filter,  and  wash  with  boiling  alcohol.  Dry  the  filter  and  its 
contents  at  a  heat  under  100°,  ignite  in  a  tared  platinum  capsule, 
cool,  and  pour  on  the  residue  a  few  drops  of  nitric  acid,  heat  to  a 
dull  red,  add  one  or  two  drops  of  sulphuric  acid,  and  heat  anew. 
Finally,  heat  the  precipitate  to  bright  redness.  If  the  cold 
residue  is  not  entirely  white,  calcine  anew  after  the  addition  of 
nitric  and  sulphuric  acid,  and  weigh  after  cooling.    From  the 


NORMAL  ELEMENTS  OF  THE  UEINE.  107 

ascertained  weight  deduct  that  of  the  capsule.  The  difference 
represents  the  weight  of  the  sulphate  of  barium,  and  this,  multi- 
plied by  0*34335  or  by  0*4206,  gives  the  proportion  of  anhydrous 
sulphuric  acid  (S03)  or  of  H2S04  contained  in  the  volume  of 
urine  analyzed. 

Quantitative  Analysis  of  the  Total  Sulphur. — Mix  50  c.c. 

of  urine  with  a  few  grammes  of  carbonate  of  soda  and  nitrate  of 
potash.  Evaporate  to  dryness  in  a  platinum  capsule.  Dissolve 
in  water,  and  expel  the  nitric  acid  by  successive  evaporations 
with  hydrochloric  acid.  Finally,  dissolve  the  residue  in  water, 
and  ascertain  the  amount  of  sulphuric  acid.  The  determined 
weighs  of  anhydrous  acid  multiplied  by  0*400  gives  the  pro- 
portion of  total  sulphur,  and  if  from  this  weight  be  subtracted 
the  acid  of  the  sulphates  and  the  sulpho- organic  acids,  the 
difference,  multiplied  by  0*400,  represents  the  sulphur  other  than 
that  in  the  state  of  sulphuric  acid. 

Sulphuric  acid  is  augmented  in  the  urine  by  large  ingestion  of 
animal  food,  of  sulphuric  acid  itself,  of  sulphur  combinations, 
the  use  of  cruciferce  (cauliflower,  turnip,  etc.).  It  is  diminished 
by  all  other  forms  of  vegetables. 

Pathological  Significance.  —  In  acute  febrile  diseases 
sulphuric  acid  is  but  feebly  augmented  in  the  urine.  In  the 
early  stages  of  typhoid  fever  it  is  little  above  the  normal  in 
amount,  while  during  convalescence  it  is  less.  In  pneumonia 
and  acute  myelitis  the  augmentation  is  considerable.  In  such 
chronic  affections  as  leukaemia,  polyuric  and  glycosuric  diabetes, 
and  progressive  muscular  atrophy,  it  is  augmented ;  in  certain 
diseases  of  the  kidney  it  is  diminished  in  the  urine. 

Phosphoric  Acid  and  Phosphates. 

Normally  the  urine  contains  phosphoric  acid  in  combination 
with  different  bases.  It  frequently  enters  into  the  composition 
of  various  calculi  and  urinary  sediments. 

Properties  of  Phosphates. — Phosphoric  acid  is  tribasic,  and 
forms  three  varieties  of  salts  :  basic  salts,  neutral  salts,  and  acid 
salts. 

Alkaline  phospliates  are  soluble  in  water,  and  insoluble  in 
alcohol;  earthy  phosphates  are  insoluble  in  water,  sparingly 


108 


THE  URINE  IN  HEALTH  AND  DISEASE. 


soluble  in  water  charged  with  carbonic  acid  gas,  insoluble  in 
alkalies,  and  very  soluble  in  mineral  acids,  in  acetic  acid,  and  in 
solutions  of  acid  salts. 

With  chlorides  of  barium  or  calcium  and  ammonia,  phosphates 
give  a  flocculent  precipitate  insoluble  in  ammonia,  but  soluble  in 
mineral  acids.  When  a  magnesium  salt  is  added  to  a  solution 
of  the  phosphates,  a  white  crystalline  precipitate  of  triple  phos- 
phate is  formed,  which  is  soluble  in  acids,  but  insoluble  in 
ammonia.  Ferric  chloride  added  to  a  solution  of  phosphates, 
containing  no  other  free  acid  but  acetic  acid,  causes  a  yellow 
flocculent  precipitate  of  ferric  phosphate. 

Mohjbdate  of  ammonia  in  nitric  acid  gives  a  yellow  pre- 
cipitate with  phosphates,  slowly  in  the  cold,  but  more  rapidly 
with  heat.  Phosphate  solutions,  on  addition  of  acetate  of  soda, 
give  with  acetate  of  uranium  a  yellow  precipitate  of  phosphate 
of  uranium,  soluble  in  mineral  acids,  but  insoluble  in  acetic  acid. 

Phosphates  of  the  Urine. — Phosphoric  acid  is  found  in  the 
urine  united  with  soda,  potash,  lime,  and  magnesia  as  bases. 

Generally  the  alkaline 
phosphates  (sodium  and 
potassium)  represent 
three  -  fourths  of  the 
amount -v  of  phosphates 


eliminated 
four  hours, 
alkaline 
phosphate 


in    twenty  - 
Of  the  two 
phosphates, 
of  sodium 


exists  in  Larger  quantity 

than  thai  of  potassium. 
These  liWO  salts  exist  in 

the  state  of  acid  phos- 
phates, and  it  is  to  them 
chiefly  that  the  acidity 
of  normal  urine  Is  due. 
Two-thirds  of  bhe  total  weightof  earthy  phosphates  (magnesium 
and  calcium)  are  represented  by  phosphate  of  magnesium)  the 

Other  third  by  phosphate  of  calcium. 

While  the  earthy  phosphates  are  insoluble  in  water,  they  are, 


Fig.  30.   Stellab  Phosphates  of  Lime. 


NOEMAL  ELEMENTS  OF  THE  UKINE. 


109 


nevertheless,  kept  in  solution  in  the  urine  by  means  of  the 
carbonic  acid  and  the  acid  salts,  especially  the  acid  phosphate  of 
sodium  contained  in  the 
urine.  "When  the  acidity  ^C^s 
of  the  urine  is  neutral- 
ized by  the  addition  of 
an  excess  of  ammonia,  or 
when  it  has  undergone 
the  ammoniacal  fermen- 
tation and  has  become 
alkaline,  the  phosphate  of 
lime,  which  is  insoluble 
in  alkaline  liquors,  is 
most  frequently  precipi- 
tated in  an  amorphous 
form,  the  phosphate  of 

magnesium      combining  FlG>  3i._Tripie  Phosphates  (Phos- 
with  the  ammonia,  and     phates  of  Ammonia  and  Magnesia). 
being  precipitated  under  the  form   of  ammomo-phosphate  of 
magnesium.    It  is  thus  that  the  earthy  phosphates  are  fre- 
quently observed  in  the 


urine  under  pathologi- 
cal conditions.  As  the 
urine  always  contains 
at  the  same  time  phos- 
phate of  calcium  and 
phosphate  of  magne- 
sium, the  sediment  is 
usually  composed  of  a 
combination  of  these 
two  phosphates. 

Sediments 
wise  produced 
the    urine  has 
rendered   alkaline,  or 
merely  neutralized  by  Fig. 
a  fixed  alkali,  such  as 
potash  or  soda,  for  example,  in  consequence  of  the  prolonged 


-Triple  Phosphates  (Feathery 
Form). 


110 


THE   UKINE  IN  HEALTH  AND  DISEASE. 


use  of  alkalies  as  therapeutic  agents.  In  this  case  the  sediment 
usually  consists  of  phosphate  of  lime. 

Phosphoglyceric  Acid. — Phosphoric  acid  may  be  found  in 
the  urine  in  combination  with  glycerine,  under  the  form  of 
pliosplw glyceric  acid.  This  acid  is  usually  found  in  cases  of 
leucocythaemia.  According  to  Lepine  and  Egmonnet,  it  is 
found  in  normal  urine  to  the  extent  of  15  milligrammes  per 
litre,  and  its  quantity  is  augmented  after  the  use  of  chloroform 
as  an  anaesthetic. 

Qualitative  Analysis  of  Phosphoric  Acid. — The  presence 
of  phosphoric  acid  in  the  urine  in  combination  with  lime  and 
magnesia  is  indicated  by  the  precipitation  of  earthy  phosphates 
by  means  of  ammonia.  In  order  to  separate  the  phosphoric 
acid  from  the  alkaline  phosphates,  filter  the  urine  precipitated 
by  the  ammonia,  and  test  the  filtered  liquid  with  magnesia 
mixture,  or  with  a  solution  of  uranium  plus  acetic  acid,  or 
with  perchloride  of  iron,  when  a  yellow  precipitate  of  uranic 
phosphate  and  a  white  precipitate  will  be  respectively  produced. 

Quantitative  Analysis  of  Phosphoric  Acid.  —  Of  the 
numerous  processes  recommended  for  this  purpose,  the  most 
rapid  is  the  volumetric  method  proposed  by  Neubauer.  It  is 
based  on  the  following  reactions :  Acetate  or  nitrate  of  uranium 
gives  with  acetic  solutions  of  phosphates  a  yellow  flocculent 
precipitate  of  constant  composition  ;  and  when  all  the  phosphoric 
acid  is  precipitated,  the  uranium  salt  added  in  excess  gives  with 
ferrocyanide  of  potassium  a  characteristic  brown  coloration. 
This  process  requires  the  following  solutions  : 

(1)  A  Standard  Solution  of  Phosjrfioric  Acid. — Dissolve  in 
distilled  water  3*087  grammes  of  dry  acid  phosphate  of  ammonia, 
and  make  up  the  solution  to  1  litre.  Fifty  c.c.  of  this  solution 
contain  0*1  gramme  of  phosphoric  acid. 

(2)  An  Acetic  Solution  of  Acetate  of  Soda. — In  a  little  water 
dissolve  100  grammes  of  pure  crystallized  acetate  of  soda,  add 
50  c.c.  of  crystallized  acetic  acid,  and  a  sufficiency  of  water  to 
make  up  to  1  litre. 

(3)  Solution  of  Ferrocyanide  of  Potassium. — A  10  per  cent, 
solution. 

(4)  A  Standard  Solution  of  Nitrateof  Uranium. — Dissolve  20 


NORMAL  ELEMENTS  OF  THE  UEINE. 


Ill 


grammes  of  pure  and  dry  oxide  of  uranium  in  as  little  nitric  acid 
as  possible.  Dilute  to  a  litre  and  determine  the  titre  as  follows  : 
Into  a  small  beaker  measure  50  c.c.  of  the  phosphoric  acid 
solution,  then  add  5  c.c.  of  the  acetate  of  soda  solution,  and 
into  the  mixture,  heated  on  a  water-bath  almost  to  ebullition, 
drop  by  means  of  a  burette  the  solution  of  uranium  until  a  pre- 
cipitate ceases  to  form.  By  means  of  a  glass  rod  put  one  drop 
of  the  liquid  on  a  fragment  of  porcelain,  and  with  a  pipette  add 
a  drop  of  the  solution  of  ferrocyanide  of  potassium.  If  no  color- 
ation is  produced,  add  to  the  liquid  ^  c.c.  of  the  solution  of 
uranium,  and  recommence  the  testing  with  the  ferrocyanide  and 
continue  until  a  reddish-brown  coloration  is  produced.  This 
being  obtained,  measure  again  50  c.c.  of  the  phosphoric  acid 
solution,  and  add  5  c.c.  of  acetate  of  soda  solution,  then  add  at 
once  a  volume  of  solution  of  uranium  equal  to  that  primarily 
employed,  less  |  c.c.  Heat  to  ebullition,  add  ^  c.c.  of  solution 
of  uranium  and  test  with  ferrocyanide  of  potassium,  continuing 
thus  until  the  reddish-brown  colour  begins  to  manifest  itself. 
Then  read  off  from  the  burette  the  volume  of  the  uranium  solution 
employed  to  obtain  the  coloration.  Supposing  the  volume  to 
be  19*8,  it  is  easy  to  determine  to  how  much  phosphoric  acid 
1  c.c.  of  the  uranium  solution  corresponds.  Since  50  c.c.  of  the 
phosphoric  acid  solution  employed  for  the  titration  contain  0*1 
gramme  of  this  acid, 

19*8  of  uranium  solution=0*l  gramme  of  phosphoric  acid, 

1  C.C.  =  X, 

hence  x=^-^  =  0*00505. 

Each  c.c.  of  the  uranium  solution  corresponds,  therefore,  to 
0*00505  gramme  phosphoric  acid.  To  estimate  the  amount  of  phos- 
phoric acid  in  the  urine,  proceed  in  the  same  manner  as  for  the 
standardization  of  the  uranium  solution.  Measure  50  c.c.  of  the 
filtered  urine,  and  add  5  c.c.  of  acetate  of  soda  solution.  Heat 
to  ebullition,  and  add  the  uranium  solution  until  a  coloration 
is  obtained  with  ferrocyanide  of  potassium.  The  number  of  c.c. 
employed  multiplied  by  0*00505  indicates  the  quantity  of  phos- 
phoric acid  contained  in  50  c.c.  of  urine,  and  this  quantity 
multiplied  by  20  gives  the  proportion  per  litre. 


112 


THE  UEINE  IN  HEALTH  AND  DISEASE. 


Freund*  proposes  the  following  method  for  estimating  the 
separate  amount  of  monobasic  and  dibasic  phosphates  when  the 
two  exist  together  in  the  urine.  The  method  is  based  on  the 
property  which  monobasic  phosphates  possess  of  forming  with 
chloride  of  barium  an  insoluble  precipitate — acid  phosphate  of 
barium.  With  a  liquid  containing  the  two  phosphates  the 
amount  of  whose  total  phosphates  is  known,  it  suffices  to  add 
chloride  of  barium  to  obtain  the  monobasic  phosphate  precipitate. 
The  phosphorus  of  the  precipitate  being  estimated,  subtract  from 
the  total  to  obtain  the  amount  of  the  dibasic  combination. 

Variations  of  Phosphoric  Acid  in  Urine.— Phosphoric  acid 
exists  in  the  urine  in  combination  with  lime,  magnesia  and  soda. 
It  is  the  acid  phosphate  of  soda  which  determines  the  acidity  of 
the  urine.  An  adult  in  good  health  using  a  mixed  dietary 
eliminates  on  an  average  from  2  to  3  grammes  of  phosphoric 
acid  in  twenty -four  hours.  This  quantity  is  augmented  when 
animal  food  preponderates  in  the  dietary,  and  also  after  the 
ingestion  of  phosphates  or  substances  rich  in  phosphates.  On 
the  other  hand,  the  phosphoric  acid  is  diminished  by  fasting 
and  by  a  vegetable  dietary.  The  excretion  of  phosphoric  acid  is 
generally  augmented  simultaneously  with  that  of  urea  and 
chlorides  as  the  result  of  an  abundant  ingestion  of  fluids. 
Excessive  intellectual  or  muscular  exertion  acts  in  a  similar 
manner. 

Pathological  Significance. — In  acute  febrile  diseases,  during 
the  first  few  days  there  is  generally  a  diminution  of  phosphoric 
acid  in  the  urine,  and  towards  the  termination  of  their  course, 
and  when  death  is  imminent,  the  diminution  is  still  more  pro- 
nounced. As  the  fever  diminishes  the  excretion  of  phosphoric 
acid  augments,  and  this  continues  during  the  whole  of  con 
valescence,  especially  when  abundant  nourishment  is  taken.  In 
these  cases,  the  amount  may  sometimes  exceed  the  normal.  In 
chronic  diseases  the  elimination  of  phosphoric  acid  depends  on 
the  functional  activity  of  the  digestive  organs.  Generally  speak- 
ing, the  earthy  phosphates  diminish  in  cerebral  affections,  rheuma- 

*  '  Ueber  eine  Method e  zur  Bestiminung  von  einfach  -Saurem 
Phosphate  neben  Zweifach •Saurem  Phosphate  in  Harn'  (Centralb.  /. 
Med.  Wi88ehsch.9  1892,  No.  38,  p.  689). 


NORMAL  ELEMENTS  OP  THE  URINE. 


113 


tism,  mollities  ossium,  rickets,  catarrh  of  the  bladder,  etc.,  while 
they  are  augmented  in  diseases  of  the  spinal  cord  and  kidneys, 
dropsy,  atrophy  of  the  liver,  and  glycosuria.  In  the  last  affec- 
tion the  phosphaturia  is  frequently  accompanied  by  azoturia. 

Tessier  has  described  a  condition  to  which  he  has  given  the 
name  of  '  diabetic  phosphaturia,'  or  '  phosphaturia,'  which  is 
accompanied  by  disorders  of  the  nervous  system  and  pulmonary 
complications.  He  considers  this  state  as  symptomatic  of  tuber- 
culosis, or  to  indicate  latent  glycosuria.  Bouchard  has  arrived 
at  the  following  conclusions  on  this  subject : 

(1)  In  the  majority  of  cases  of  diabetic  glycosuria,  and  especi- 
ally in  cases  of  moderate  gravity,  with  a  small  elimination  of 
sugar  and  urea,  phosphates  are  eliminated  in  a  normal  amount, 
or  even  to  a  less  extent  than  normal. 

(2)  The  augmentation  of  the  glycosuria  may  be  accompanied 
by  a  parallel  augmentation  of  phosphates. 

(3)  When  disassimilation  is  augmented  in  the  diabetic,  and 
the  sugar  is  above  the  normal  in  quantity,  this  disassimilation 
takes  place  at  the  expense  of  the  tissues  which  furnish  the  urea 
and  the  phosphoric  acid,  so  that  azoturia  accompanies  the  phos- 
phaturia, and  vice  versa. 

(4)  The  parallelism  between  the  elimination  of  the  urea  and 
that  of  the  phosphates  takes  place  only  in  the  cases  in  which  the 
elimination  is  above  the  normal.  Anazoturia  may  be  observed 
with  a  normal  elimination  of  phosphates,  an  I  hypophosphaturia 
with  a  normal  excretion  of  urea. 

(5)  It  appears  that  phosphaturia  is  far  from  bein^  the  rule  in 
saccharine  diabetes. 

When  phosphates  deposit  in  the  urine,  a  short  time  after 
emission  it  assumes  a  milky  appearance.  At  the  moment  of 
emission  it  is  clear.  Heat  precipitates  the  phosphates,  which 
are  dissolved  by  a  drop  or  two  of  acetic  acid. 

Microscopic  examination  shows  the  characteristic  forms  of 
phosphates. 

Potash,  Soda,  Lime,  Magnesia. 

These  bases  exist  in  the  urine  in  tli3  form  of  chlorides,  sul- 
phates, and  phosphates. 

8 


114 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


Potash  and  Soda. — A  healthy  man,  on  a  mixed  diet,  elimi- 
nates in  twenty-four  hours  2  to  3  grammes  of  potash,  and  4  to 
6  grammes  of  soda.  In  febrile  affections  the  excretion  of  potash 
is  three  or  four  times  greater  ;  while  that  of  the  soda  diminishes 
when  the  fever  is  at  its  height,  but  rapidly  augments  during  its 
decline.  After  the  ingestion  of  potash  and  soda  salts,  the  urine 
presents  a  notable  augmentation  in  fixed  alkalies. 

Qualitative  Analysis. — To  100  c.c.  of  urine  add  a  little 
hydrochloric  acid,  and  then  two  volumes  of  a  clear  mixture  of. 
equal  parts  of  alcohol  and  ether,  with  a  little  chloride  of  platinum. 
After  a  few  hours  there  are  deposited  crystals  of  chloride  of 
platinum  and  potassium,  mixed  with  chloride  of  platinum  and 
ammonia,  whose  octahedral  form  is  characteristic.  In  the  case 
of  soda,  evaporate  the  urine  in  a  water-bath  until  crystallization 
takes  place.  A  portion  of  the  crystalline  mass,  introduced  into 
gas-flame,  imparts  to  it  an  intense  yellow  colour,  whose  spectrum 
exhibits  a  yellow  ray  coinciding  with  the  line  D  of  the  solar 
spectrum. 

Quantitative  Analysis. — The  weight  of  the  double  chloride 
of  platinum  and  potassium  multiplied  by  0*3051  gives  the 
weight  of  the  chloride  of  potassium ;  the  difference  represents 
the  weight  of  the  chloride  of  sodium.  To  obtain  the  quantity  of 
potash  and  soda  multiply  the  weight  of  the  chloride  of  potassium 
by  0*6317,  and  by  0*5302,  the  weight  of  the  .chloride  of 
sodium. 

Lime  and  Magnesia. — According  to  Neubauer,  a  healthy  man 
excretes  between  0*12  and  0*25  gramme  of  lime  in  twenty-four 
hours,  and  from  0*18  to  0*28  gramme  of  magnesia  in  the  same 
time.  Lime  and  magnesia  exist  in  normal  urine  under  the  form 
of  phosphates,  and  in  pathological  urine  as  sulphates,  oxalates, 
and  urates. 

The  presence  of  lime  and  magnesia  is  thus  demonstrated : 
Precipitate  the  urine  by  ammonia  ;  dissolve  the  precipitate, 
which  is  a  mixture  of  basic  phosphate  of  lime  and  of  ammonio- 
phosphate  of  magnesia,  in  acetic  acid ;  then  add  a  small  portion 
of  chloride  of  ammonium,  and  finally  a  solution  of  oxalate  of 
ammonia,  by  which  the  lime  is  precipitated  in  the  form  of 
oxalate,  while  the  magnesia  remains  in  solution.    To  demon- 


NORMAL  ELEMENTS  OF  THE  URINE. 


115 


strate  the  latter,  add  ammonia  to  the  filtered  liquid,  when  a  pre- 
cipitate of  the  triple  phosphate  results. 

Quantitative  Analysis. — The  weight  of  the  triple  phosphate 
precipitate  multiplied  by  0*3604  gramme  gives  the  weight  of 
magnesia.  To  ascertain  the  weight  of  lime,  precipitate  100  c.c. 
of  urine  with  ammonia.  Eedissolve  the  precipitate  in  acetic 
acid,  and  add  a  sufficiency  of  amnionic  oxalate  to  precipitate  all 
the  lime  as  oxalate.  Allow  the  precipitate  to  settle,  separate  by 
nitration,  ignite  with  the  filter  in  a  platinum  crucible,  when 
calcic  oxide  and  carbonate  result.  Transfer  to  a  flask  by  aid  of 
a  washing  bottle,  and  add  an  excess  of  ^  nitric  acid.  Determine 
the  amount  of  acid  above  what  is  required  to  saturate  the  lime 
by  ^  caustic  alkali,  each  c.c.  of  which  is  equal  to  0*0028 
gramme  CaO. 

Ammonia. 

According  to  Neubauer,  normal  urine  at  the  moment  of  emis- 
sion contains  a  small  quantity  of  ammonia,  in  the  form  of 
carbonate,  chloride,  etc.,  amounting  to  0*6  to  0*8  in  twenty-four 
hours.  This  ammonia  results  from  the  food,  the  liquids  ingested, 
and  the  inspired  air. 

Qualitative  and  Quantitative  Analysis.  (See  Abnormal 
Constituents  of  the  Urine.) 

Variations  in  the  Proportion  of  Ammonia  in  the  Urine. — 
Ammonia  is  augmented  in  the  urine  by  a  dietary  rich  in  animal 
food,  and  the  ingestion  of  ammoniacal  compounds,  which  pass, 
into  the  urine  without  undergoing  alteration,  such  as  the  salts 
with  mineral  acids,  or  of  vegetable  acids  which  are  transformed 
into  carbonates.  In  disease  the  amount  of  ammonia  in  the 
urine  is  above  the  normal.  In  catarrh  of  the  bladder  the  urine 
contains  ammonia  in  the  form  of  carbonate,  arising  from  the  • 
decomposition  of  urea  in  the  bladder. 


116  THE  UKINE  IN  HEALTH  AND  DISEASE. 


Iron,  Nitric  Acid  and  Nitrates  and  Nitrites,  Silica,  Per- 
oxide of  Hydrogen. 

Iron. — Iron  is  eliminated  in  healthy  urine,  according  to 
Magnier,  to  the  extent  of  3  to  11  milligrammes  per  litre  in 
twenty-four  hours. 

Analysis.  (See  Medicaments  and  Accidental  Elements  of 
the  Urine.) 

Nitrates  and  Nitrites. — The  presence  of  nitrates,  arising  from 
certain  principles  of  food,  has  been  demonstrated  by  Schonbein 
in  the  urine.  Potable  waters,  peas,  salads,  etc.,  contain  small 
quantities  of  nitrates.  Under  the  influence  of  putrefaction  in 
urine  undisturbed,  the  nitrates  are  transformed  into  nitrites.  In 
order  to  demonstrate  the  presence  of  nitrates,  evaporate  a  little 
urine  to  dryness  with  a  little  potash,  and  treat  the  residue  with 
sulphuric  acid.  Nitrous  vapours  are  evolved,  which  impart  a 
blue  colour  to  iodide — starch  paper.  If  the  urine  be  not  fresh, 
and  if  the  nitrates  have  been  transformed  into  nitrites,  the 
presence  of  the  latter  is  demonstrated  by  adding  to  the  urine  a 
little  solution  of  starch  and  iodide  of  potassium,  and  then  a  few 
drops  of  water  acidulated  with  sulphuric  acid,  when  a  blue 
coloration  results. 

Silica. 

To  extract  silica  from  urine,  dissolve  in  a  platinum  crucible 
with  an  excess  of  carbonate  of  potassium  and  sodium  the 
incinerated  residue  of  from  two  to  three  litres  of  urine.  Acidu- 
late with  hydrochloric  acid,  and  evaporate  to  dryness  on  a  water 
bath.  Treat  the  residue  again  with  hydrochloric  acid  and  water, 
when  the  silica  is  found  to  remain  in  the  form  of  a  white,  taste- 
less, and  odourless  powder,  soluble  in  a  boiling  solution  of 
carbonate  of  soda.  The  quantity  of  silica  voided  with  the  urine 
in  twenty-four  hours  varies  from  0*02  to  0*03  gramme. 

Peroxide  of  Hydrogen  has  been  shown  by  Schonbein  to  exist 
in  normal  urine.  Its  presence  is  demonstrated  thus :  Add  to 
200  c.c.  of  fresh  urine  a  few  drops  of  a  solution  of  sulphate  of 
indigo,  so  as  to  obtain  a  green  coloration,  and  finally  a  small 
portion  of  a  solution  of  the  sulphate  of  protoxide  of  iron.    If  the 


NORMAL  ELEMENTS  OF  THE  URINE. 


117 


urine  contains  peroxide  of  hydrogen,  the  colour  of  the  mixture 
changes  from  clear  to  brownish-yellow,  in  consequence  of  the 
discoloration  of  the  indigo. 

Gases  in  the  Urine. 

Carbonic  Acid,  Oxygen,  Nitrogen. — The  urine  always  con- 
tains in  solution  carbonic  acid,  oxygen  and  nitrogen.  According 
to  Morin,  a  litre  of  normal  urine  contains  15*957  c.c.  of  carbonic 
acid,  0*658  c.c.  of  oxygen,  and  7*773  c.c.  of  nitrogen.  All  causes 
which  accelerate  respiration  increase  the  amount  of  carbonic 
acid  and  nitrogen,  and  diminish  that  of  oxygen.  The  com- 
bined portion  of  the  carbonic  acid  is  united  to  the  alkalies  and 
earthy  salts  in  the  form  of  bicarbonates.  Its  quantity  is  aug- 
mented in  fevers  pari  passu  with  that  of  urea.  Carbonic  acid 
aids  the  solution  in  the  urine  of  earthy  phosphates. 


PART  III. 


CHAPTER  IV. 
ABNORMAL  CONSTITUENTS  OF  THE  URINE. 

ORGANIC  SUBSTANCES — INORGANIC  SUBSTANCES — ORGANIZED  SUB- 
STANCES. 

Classification  of  Albumens — Properties  of  Albumen — Coagulation  by 
Heat — Coagulation  by  Nitric  Acid — Tests  for  Albumen  — Fallacies 
in  Heat  Test — The  Nitric  Acid  Test — Fallacies  in  Nitric  Acid  Test 
— Tanret's  Reagent — Picric  Acid  Test — Feirocyanide  of  Potassium 
Test  —  Nitro-prussiate  of  Soda  Test  —  Sodium  Tungstate  Test  — 
Spiegler's  Test — Stutz's  Test — Roch's  Test — Jaworowski's  Test — 
Other  Tests  for  Albumen— Mixed  Albuminuria — Relative  Value 
and  Delicacy  of  Various  Albumen  Tests— Quantitative  Analysis — 
Process  of  Tanret  and  Troyes — Bbdeker's  Method — Process  of 
Brandberg — Esbach's  Process — Zahor's  Method — Pathological  Sig- 
nificance— Therapeutic  Indications — Purulent  Albuminous  Urine — 
Globuline — Qualitative  and  Quantitative  Analysis  —  Process  of 
Hammarstein — Pathological  Significance — Fibrine — Mucine— Pro- 
perties of  Mucus — Analysis — Leucomaines  and  Ptomaines — Pep- 
tones—  Properties  of  Peptoms  -Analysis — Process  of  Hofmeister  — 
Reaction  with  Tanret's  Solution — Other  Reactions— Pathological 
Significance —  Hemi-albumose —  Properties  —  Analysis  —  Transitory 
Albuminuria — Pathological  Significance. 

The  abnormal  constituents  of  the  urine  may  be  considered  as 
consisting  of  three  groups,  viz. :  (1)  Elements  of  an  Organic 
Nature  ;  (2)  Elements  of  a  Mineral  or  Inorganic  Nature ; 
and  (8)  Organized  Substances. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  119 


ORGANIC  SUBSTANCES. 

Albumen. 

Peptones. 

Glucose. 

Levulose. 

Lactose. 

Inosite. 

Cystine. 

Tyrosine. 

Leucine. 

Acetone. 

Melanine. 

Diverse  acids. 

Bile  elements. 

Fatty  matter. 

Tube-casts. 


INORGANIC  SUBSTANCES. 

Salts  of  ammonia  (carbonate  of 
ammonia,  ammonio  -  phos- 
phate of  magnesia,  urate  of 
ammonia). 

Sulphuretted  hydrogen. 

ORGANIZED  SUBSTANCES. 

Blood  corpuscles  (haemoglob- 
ine). 

Leucocytes  (pus). 
Mucus. 

Epithelial  cells. 

Spermatozoa. 

Infusoria. 


Organic  Substances. 

Albumen. 

C36H56N90iiS  (Lieberkhiin). 

Carbon    ...       ...       ...       ...  53  per  cent. 

Hydrogen   7 

Nitrogen  ...       ...       ...       ...  15*50  ,, 

Oxygen   23 

Sulphur   1-50  „ 

100-00 

Albumen  is  primarily  synthetically  formed  by  plants.  It  is 
introduced  into  the  animal  organism  as  food,  and  there  under- 
goes important  and  varied  modifications  before  being  in- 
corporated with,  and  forming  part  of,  the  living  tissue.  It  exists 
in  greatest  abundance  in  blood-plasma.  It  likewise  forms  an 
important  constituent  of  lymph  and  chyle,  of  serous  fluids,  and 
of  the  other  textures  of  the  body.  It  exists  in  large  quantity  in 
the  egg,  and  this  form  of  albumen  is  usually  regarded  as  the 
standard  of  albuminous  substances,  other  forms  of  albumen 
being  classed  in  the  degree  of  their  constituent  relationship  to 
this  variety.    Other  proteids  exist  in  animal  tissues,,  which  have 


120 


THE  URINE  IN  HEALTH  AND  DISEASE. 


important  relations  to  the  pathology  and  diagnosis  of  disease. 
The  entire  group  may  be  thus  classified  : 

Class  I.-Native  Albumen    ...  j  \  ff^X^en. 

1.  Acid  albumen  or  syntonin. 
Class  II. — Derived  Albumens  {  2.  Alkali  albumen. 

3.  Casein. 

1.  Globulin  (crystallin). 

2.  Paraglobulin  (fibrinoplastin, 

serum  globulin). 
Class  III.-Globulins  -^.Fibrinogen 

4.  Myosin. 

5.  Vitallin. 

Class  IV. — Fibrin  (  Mucin. 

Class  V.—  Coagulated  Proteids  (  Leucomaines,  Ptomaines. 
Class  VI.-Peptones  \  P^apeptone-Hemialbu- 


mose  or  Propeptone 
Class  VII. — Lardacein  or  Amyloid  Substances.* 

According  to  Hoppe-Seyler,  the  composition  of  the  foregoing 
varies  from  C  51*5,  H  6'9,  N  15'2,  S  0*3,  0  209  to  C  54*5,  H  7'3, 
N  17*0,  S  20,  0  23-5. 

Properties  of  Albumen. — Albumen  exists  in  a  soluble  and  in 
an  insoluble  form.  In  the  former  condition  it  exists  in  all  the 
fluids  and  tissues  of  the  body,  and  in  vegetables.  It  is  convertible 
into  the  latter  form  by  boiling  with  water,  by  absolute  alcohol, 
acids,  and  strong  alkalies.  On  incineration  it  evolves  nitrogen ; 
and  heated  in  a  tube  with  caustic  potash,  ammonia  is  given  off, 
which  may  be  recognised  by  its  action  on  litmus  paper,  and  the 
formation  of  white  fumes  on  coming  in  contact  with  hydrochloric 
acid.  Dried,  it  forms  as  an  inodorous,  insipid,  and  slightly 
yellow  amorphous  substance,  soluble  in  water,  but  insoluble  in 
alcohol. 

The  presence  of  sulphur  in  albumen  may  be  thus  demonstrated. 
Boil  albumen  with  a  solution  of  caustic  soda.  A  sulphide  of  soda 
is  formed  which  gives  a  black  precipitate  with  a  salt  of  lead,  or 

*  For  detailed  relations  of  the  foregoing  the  reader  is  referred  to 
special  works. 


ABNORMAL  CONSTITUENTS  OF  THE  UBINE.  121 


by  calcining  a  quantity  of  albumen  with  caustic  potash  and  nitrate 
of  potash  in  a  porcelain  crucible,  a  sulphate  of  potash  is  produced, 
easily  recognised  by  the  action  of  chloride  of  barium.  From  an 
aqueous  solution  albumen  is  precipitated  by  alcohol,  which, 
according  to  the  nature  of  the  precipitate,  may  be  redissolved  in 
whole  or  in  part.  Albumen  is  coagulated  by  all  the  mineral  acids 
with  the  exception  of  ortho-  and  pyrophosphoric  acid.  It  is  coagu- 
lated without  combination  by  carbolic  acid,  picric  acid,  nitric  acid, 
sulphuric  acid,  and  tannic  acid.  Concentrated  hydrochloric  acid, 
especially  with  the  addition  of  a  little  sulphuric  acid,  dissolves  a 
small  portion  of  the  albumen,  and  imparts  to  the  remainder  an 
intense  blue  colour  which  persists  a  long  time.  Nitric  acid 
causes  serum-albumen  to  become  yellow,  and  on  the  addition  of 
ammonia  a  deep  orange  colour  is  the  result.  This  is  the  xantJw- 
proteic  reaction. 

A  solution  of  mercurous  and  mercuric  nitrates,  made  by  dis- 
solving one  part  of  mercury  in  two  parts  of  nitric  acid  and 
four  parts  of  water,  imparts  a  deep-red  colour  to  albumen  in 
either  the  solid  or  liquid  form  when  the  mixture  is  warmed  from 
60°  to  100°  Cent.  (Millon's  reaction).  As  a  test,  this  is  not 
applicable  to  the  urine,  as  four  different  precipitates  are  formed 
by  it.  Bichloride  of  mercury  readily  precipitates  albumen  from 
solution,  the  precipitate  being  soluble  in  an  excess  of  albumen. 
It  is  likewise  precipitated  by  nitrate  of  silver,  acetate  of  lead, 
tannin,  creosote,  aniline,  etc.  It  is  not  precipitated  by  formic 
acid,  tartaric  acid,  nor  acetic  acid,  the  last  of  which  separates 
proteine.  Potash,  soda,  and  the  carbonates  of  these  bases  dissolve 
albumen,  and  prevent  its  coagulation  by  heat. 

Sulphuric  ether  coagulates  egg  albumen.  The  albumen  of  the 
serum  is  not  so  coagulated. 

Coagulation  of  Albumen  by  Heat.— If  a  solution  of  albumen, 
neutral  or  acid,  be  heated  to  a  temperature  of  62°  Cent.  (94° 
Fahr.),  it  begins  to  become  cloudy  owing  to  the  separation  of 
albumen ;  at  a  temperature  of  72°  to  75°  Cent.  (104°  to  107°  Fahr.) 
the  coagulation  is  complete.  The  more  dilute  the  solution  of 
albumen,  the  higher  is  the  temperature  required.  The  precipitate 
thus  formed  is  insoluble  in  water  or  in  a  moderate  quantity  of 
nitric   acid.     The  point  of  coagulation  by  heat  is  modified 


122  THE  URINE  IN  HEALTH  AND  DISEASE. 

by  certain  acid  salts  and  some  alkalies.  Thus,  sulphate  of 
magnesia  and  sulphate  of  soda  have  jper  se  no  effect  upon 
albumen,  but  when  the  albuminous  solution  is  saturated  by 
them,  the  point  of  coagulation  is  lowered  to  50°  Cent.  (82°  Fahr.). 
It  is  important  to  keep  this  in  view  in  testing  for  very  minute 
quantities  of  albumen.  Should  the  albuminous  solution  be 
alkaline,  and  especially  if  the  quantity  of  albumen  be  small, 
coagulation  on  heating  does  not  take  place.  It  is,  therefore, 
indispensable,  under  such  circumstances,  previously  to  acidulate 
the  urine,  or  at  least  to  render  it  neutral,  and  for  this  purpose  it 
is  necessary  to  employ  an  acid  which  does  not  coagulate  albumen, 
such  as  acetic  acid.  "When  the  urine  is  alkaline,  the  acetic 
acid  must  be  sparingly  added,  otherwise  the  albumen  is  not 
precipitated  by  heat.  Sulphate  of  soda  added  to  a  solution  of 
albumen,  acidified  by  acetic  acid,  gives  a  precipitate  of  albumen 
on  heating.  Traces  of  albumen  may  thus  be  detected  by  satu- 
rating the  urine  with  sulphate  of  soda,  acidif3Ting  with  acetic 
acid,  filtering,  and  heating  in  a  test-tube.  It  is  important  to 
note  that  urine  containing  semen,  acidulated  with  acetic  acid, 
gives  a  precipitate  on  being  heated,  the  precipitate  dissolving  on 
the  addition  of  an  excess  of  the  acid. 

Coagulation  of  Albumen  by  Nitric  Acid.  —  Nitric  acid 
coagulates  albumen  without  combining  with  it.  If  it  be  added 
drop  b}'  drop  to  albuminous  urine,  a  white  cloud  of  albuminous 
substance  is  the  result,  which  disappears  on  agitation.  If 
in  excess  the  precipitate  is  rcdissolved.  If  about  a  tenth  or  a 
fifth  of  the  volume  of  urine  be  added  of  the  acid,  a  copious  and 
persistent  white  precipitate  is  the  result.  This  precipitate  par- 
takes sometimes  of  a  colour  derived  from  the  oxidation — a  pink 
colour — of  uroerythrine,  and  sometimes,  though  rarely,  of  indigo. 

Tests  for  Albumen  in  the  Urine. 

Coagulation  of  Albumen  by  Heat.— At  a  temperature  of 
from  60°  to  100°  Cent,  albumen  contained  in  urine  is  coagulated. 
To  ensure  the  greatest  possible  accuracy  in  testing  for  albumen 
by  means  of  heat,  the  following  precautions  should  be  observed : 
The  urine  should  be  that  passed  after  breakfast,  as  frequently 


ABNORMAL  CONSTITUENTS  OF  THE  UEINE.  123 

the  urine  passed  after  resting  and  abstinence  from  food  is  free 
from  albumen,  while  containing  it  after  food  and  exercise.  If 
the  urine  be  acid,  as  it  naturally  is,  it  is  not  necessary  to  acidulate 
it ;  but  if  it  be  alkaline,  just  sufficient  acetic  acid  should  be  added 
to  render  it  acid.  In  order  to  separate  globulin,  chloride  of 
sodium  or  sulphate  of  magnesia  should  be  added,  and  the  urine 
filtered.  A  test-tube  is  then  half  filled  with  the  clear  urine,  and 
the  fluid  is  to  be  freely  boiled.  If  albumen  be  present,  and  the 
circumstances  of  light,  etc.,  favourable,  the  characteristic  flaky 
albuminous  precipitate  is  easily  recognised.  It  is  better  to  boil 
simply  the  upper  stratum  of  the  fluid,  as  in  this  manner  the 
contrast  between  the  two  portions,  especially  against  a  dark 
background,  reveals  the  smallest  trace.  This  precipitate  is 
unaffected  by  a  small  quantity  of  acetic  or  nitric  acid,  but  is 
redissolved  by  an  excess  of  them. 

Fallacies  in  the  Heat  Test. — A  modification  of  albumen  is 
met  with  occasionally  which  is  not  coagulated  by  heat.*  Certain 
important  precautions  have  to  be  observed  in  the  treating  of 
albuminous  urine  with  acetic  acid,  in  order  to  obtain  a  satisfac- 
tory precipitate  by  means  of  heat.  If  more  acetic  acid  be  added 
than  is  necessary  to  neutralize  the  free  alkali  and  slightly  acidu- 
late the  fluid,  boiling  may  produce  a  mere  cloudiness.  If  more 
acid  be  then  added,  and  the  urine  boiled,  it  becomes  perfectly 
clear.  If  at  first  the  acid  be  added  in  considerable  quantity — for 
instance,  to  the  extent  of  about  a  fourth— the  fluid  is  unaffected 
by  boiling,  and  then  the  addition  of  nitric  acid  does  not  cause 
precipitation  of  the  albumen. 

Alkaline  albuminous  urine  is  not  precipitated  by  heat,  but  the 
subsequent  addition  to  it  of  nitric  acid  causes  a  precipitate  of 
albumen.  In  alkaline  urine  the  albumen  exists  as  an  albuminate 
of  potash.  Phosphates  of  lime  or  magnesia  are  thrown  down  by 
heat,  and  turbidity  results  from  the  escape  of  carbonic  acid. 
This  precipitate  is  distinguishable  from  albumen  by  being  im- 
mediately dissolved  by  the  addition  of  a  few  drops  of  acetic  or 
nitric  acid.  Albuminous  urine  to  which  a  drop  or  two  of  nitric 
acid  may  have  been  added  accidentally,  or  purposely  for  the  sake 

*  Annal.  des  Malad.  des  Organ.  Genit.  Urin.,  1888,  p.  213,  and 
Ibid.,  1889,  p.  703. 


124 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


of  experiment,  is  not  coagulated  by  heat.  In  this  case  the 
albumen  had  been  converted  into  a  nitrate  of  albumen. 

Urine  containing  pus  is  necessarily  coagulated  by  heat.  Urine 
containing  mucin  is  not  coagulated  by  heat,  but  the  addition  of 
acetic  acid  precipitates  the  mucin.  Acetic  acid  also  throws  down 
cystin,  and  uric  acid  when  in  excess. 

The  Nitric  Acid  Test. — In  proceeding  to  test  for  albumen 
in  urine  by  means  of  nitric  acid,  the  urine  should  be  rendered 
slightly  acid  by  means  of  a  few  drops  of  acetic  acid,  and 
filtered.  Cystin  and  mucin,  if  present,  are  thus  separated. 
Two  or  three  drachms  of  the  filtered  solution  are  then  placed  in 
a  conical  glass  or  test-tube.  By  means  of  a  pipette,  a  small 
quantity  of  pure,  colourless  nitric  acid  is  allowed  to  trickle 
down  on  the  side  of  the  glass,  and  thus  mingle  with  the  urine. 
The  acid,  having  a  higher  specific  gravity,  passes  under  the  urine, 
and  at  the  junction  of  the  two  fluids  a  sharp  white  band  or  zone 
forms,  varying  in  size  with  the  quantity  of  albumen  present. 
The  acid  may  be  first  placed  in  the  glass,  and  the  urine  subse- 
quently added,  but  the  result  is  identical.  The  precipitate  of 
albumen  formed  by  the  first  few  drops  of  acid  is  redissolved  on 
shaking  the  fluid,  but  reappears  and  increases  by  further  addition 
of  acid,  and  does  not  disappear  on  being  heated.  Should  the 
precipitate  disappear  on  heating,  it  would  be  due  to  uric  acid, 
urea,  copaiba,  etc.  Not  more  than  from  a  tenth  to  a  fifth  of 
nitric  acid  should  be  added  to  the  urine. 

If  the  urine  be  rich  in  colouring  matter,  as  in  fever,  at  the  line 
of  junction  of  the  fluids  certain  shades  of  colour  may  be  formed, 
a  red  colour  resulting  from  the  presence  of  uroerythrine,  a  blue 
due  to  indigo,  a  rose-red  to  indican,  a  brownish-red  to  blood 
colouring  matter,  and  a  green  to  undecomposed  biliary  con- 
stituents. The  albumen  itself  partakes  to  a  greater  or  less  degree 
of  these  colours,  according  to  circumstances. 

Fallacies  in  the  Application  of  the  Nitric  Acid  Test. — 
With  urine  rich  in  urea,  such  as  that  of  the  dog,  nitric  acid  gives 
a  precipitate  of  nitrate  of  urea,  which  is  much  less  soluble  than 
urea,  especially  in  acid  solutions.  The  precipitate  is  distinguished 
from  albumen  by  its  crystalline  form,  by  its  solubility  on  the 
addition  of  a  small  quantity  of  water,  by  the  fact  that  more  or 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  125 

less  effervescence  takes  place  when  the  nitric  acid  is  added, 
arising  from  the  partial  decomposition  of  urea,  that  it  is  readily 
dissolved  by  heat,  and,  finally,  that  it  forms  higher  up  in  the 
tube  than  the  line  of  contact  of  the  two  liquids,  and  that  the 
precipitate  does  not  appear  until  after  the  lapse  of  a  considerable 
interval.  It  first  appears  as  a  thin  layer  on  the  surface,  and 
gradually  thickens  and  extends  from  above  downwards. 

Urates  are  decomposed  by  the  addition  of  nitric  acid,  and  a 
precipitate  of  uric  acid  is  thus  caused,  which  may  be  mistaken 
for  albumen  owing  to  its  amorphous  appearance.  Slight  heating 
causes  the  uric  acid  to  disappear ;  and  on  operating  on  a  fresh 
specimen  of  urine,  a  precipitate  is  found  to  be  occasioned  by 
acids  which  do  not  coagulate  albumen,  such  as  phosphoric  and 
acetic  acid. 

If  the  urine  contain  a  large  quantity  of  carbonic  acid,  as 
arising  from  alkaline  decomposition,  and  either  in  a  free  state  or 
combined  with  ammonia,  or  potassium,  or  sodium,  as  from  the 
administration  of  alkaline  carbonates,  or  salts  of  the  vegetable 
acids,  such  as  citrates,  tartrates,  malates,  etc.,  the  addition  of 
nitric  acid  causes  its  liberation  with  effervescence.  "While  under 
ordinary  circumstances  this  does  not  interfere  with  the  nitric 
acid  test,  it  may  so  happen,  as  when,  for  instance,  the  quantity 
of  carbonate  of  ammonia  is  very  large,  that  the  effervescence  is 
such  as  completely  to  nullify  the  test.  Again,  in  such  a  case, 
the  amount  of  acetic  acid  necessary  to  neutralize  and  acidify  is 
so  large  as  permanently  to  hold  the  albumen  in  solution.  Alka- 
line urines  are  always  more  or  less  opaque,  owing  to  the  presence 
of  amorphous  phosphates  and  bacteria,  and  cannot  be  sufficiently 
cleared  by  filtration.  To  obviate  this  difficulty,  Hoffmann  and 
Ultzmann  recommend  the  following  process :  To  the  urine  add 
about  a  fourth  of  its  volume  of  liquor  potassae ;  warm  the  mix- 
ture and  filter.  Should  the  filtrate  be  not  quite  clear,  a  few 
drops  of  the  following  solution  should  be  added:  magnesium 
sulphate  and  ammonium  chloride  of  each  one  part,  distilled 
water  eight  parts,  and  pure  liquor  ammoniee  one  part.  The  fluid 
thus  becomes  clear,  and  the  presence  of  albumen  may  be  demon- 
strated by  the  use  of  acetic  and  nitric  acid,  or  the  ierrocyanide 
of  potassium  test.    When  the  urine  contains  resinous  substances. 


!6 


THE  URINE  IN  HEALTH  AND  DISEASE. 


such  as  copaiba  or  turpentine,  the  addition  of  nitric  acid  deter- 
mines a  yellowish- white  precipitate,  which  is  dissolved  by  heating 
and  excess  of  nitric  acid.  This  substance  is  distinguished  from 
albumen  by  its  characteristic  odour,  by  its  solubility  in  alcohol, 
and  by  the  fact  that  it  is  not  precipitable  by  heat.  If  the  urine 
be  previously  heated,  the  nitric  acid  does  not  precipitate  the 
resin. 

Tanret's  Reagent. — The  double  iodide  of  potassium  and 
mercury,  prepared  as  under,  has  been  recommended  by  M. 
Tanret,  of  Paris,  as  a  delicate  test  for  albumen : 

Iodide  of  potassium      ...  ...  ...  ...  3*32  gr. 

Bichloride  of  mercury  ...  ...  ...  ...  1*35  gr. 

Acetic  acid        ...       ...  ...  ...  ...  20  c.c. 

Distilled  water,  q.s.  ad  ...  ...  ...  64  c.c. 

This  test  it  employed  in  the  ordinary  manner,  and  is  one  of 
extreme  sensibility.  A  weighty  objection  to  it  is  that  it  precipi- 
tates alkaloids  in  the  urine,  and  albumen,  or  some  other 
albuminous  substance,  apart  from  any  morbid  process  or  mani- 
festation of  ill-health.  Thus,  M.  Chateaubourg,  in  701  examina- 
tions of  the  urine  of  healthy  persons,  found  '  albuminuria '  in  no 
less  than  592  instances,  employing  this  test ;  and  Dr.  Dickinson, 
in  every  one  of  100  consecutive  cases  which  presented  them- 
selves in  hospital  and  private  practice,  in  many  of  which  *  there 
was  no  reason  to  doubt  that  the  urine  was  absolutely  natural.' 
Tanret's  solution  likewise  causes  a  cloudiness  in  the  urine  when 
urates  exist  in  excess.  This  disappears  on  heating,  to  reappear 
on  cooling.  If  the  urine  be  'previously  heated,  Tanret's  solution 
does  not  precipitate  the  urates.  It  precipitates  peptones  and 
globuline  in  the  urine,  and  is  a  more  delicate  test  for  these  than 
picric  acid,  but,  unlike  the  precipitate  with  picric  acid,  that  with 
mercuric  iodide  is  not  dissolved  on  the  application  of  heat. 
Jaccoud*  gives  the  following  caution  regarding  Tanret's  solution : 
'  I  insist  the  more  readily  on  the  causes  of  error  arising  from  the 
employment  of  Tanret's  solution,  seeing  that  it  is  so  much  used 
in  France,  and  that  I  have  been  long  struck  with  its  drawbacks. 
It  is  too  powerful  or  too  delicate.  It  precipitates  many  other 
principles  besides  true  albumen  or  serine,  and  I  cannot  help 

*  Clinique  Medical,  1886. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  127 

observing  that  it  has  been  since  its  vulgarization  (in  France) 
that  albuminuria  in  the  apparently  healthy  has  been  so  frequently 
discovered.  Possessing  the  property  of  coagulating  all  proteic 
substances  (not  to  speak  of  alkaloids),  I  am  convinced  that  many 
of  those  cases  presented,  in  reality,  nothing  in  common  with  true 
albuminuria  or  serinuria.  From  this  point  of  view,  nitric  acid  and 
heat  are  the  most  certain  reagents.  Remove  the  globuline  with 
sulphate  of  magnesia,  filter,  and  treat  the  nitrate  with  heat  and 
nitric  acid  or  the  acetic  solution  of  ferrocyanide  of  potassium. 
If  a  precipitate  result,  it  is  certain  to  be  one  of  serum  albumen. 
The  same  fluid,  treated  by  Tanret's  solution,  is  as  likely  to  give 
a  precipitate  of  peptones  as  albumen.'  The  precipitate  which 
Tanret's  solution  gives  with  albumen  is  not  dissolved  on  heating. 
It  is  also  insoluble  in  alcohol.  It  is  thus  distinguished  from 
peptones  and  alkaloids. 

Picric  Acid  Test. — Picric  acid  was  first  suggested  as  an 
albumen  test  by  M.  Gallipe.  A  saturated  solution  of  this  acid 
added  to  urine  is  a  delicate  test  for  albumen.  Such  solution  is 
slightly  heavier  than  distilled  water,  so  that,  unlike  nitric  acid, 
it  has  a  tendency  to  float  on  the  surface  of  the  urine.  When  the 
urine  is  alkaline,  the  addition  of  a  drop  or  two  of  acetic  acid 
renders  the  test  more  delicate.  The  precipitate  so  formed  is 
insoluble  by  boiling.  The  coagulum  formed  with  picric  acid  in 
cold  urine  requires  a  large  excess  of  water  for  its  solution.  It  is 
readily  dissolved  by  caustic  potash  and  ammonia,  so  that  if  the 
urine  be  alkaline,  it  should  be  acidified,  or  rendered  neutral, 
before  applying  the  test. 

The  objections  to  the  picric  acid  test  are  the  following :  It 
throws  down  creatinine,  copaiba,  peptones,  mucin,  quinine,  cin- 
chonidine,  morphia,  atropia,  and  most  other  vegetable  alkaloids ; 
but  these  precipitates,  unlike  that  caused  by  albumen,  disappear 
on  the  application  of  heat,  and  reappear  as  a  cloud  on  cooling.  On 
microscopic  examination,  as  pointed  out  by  Dr.  George  Johnson* 
the  peptones  present  a  homogeneous  appearance,  and  are  free 
from  solid  particles,  while  the  precipitate  of  the  vegetable 
alkaloids  is  finely  granular.  When  peptones  which  have  been 
dissolved  by  heat  are  precipitated  on  cooling,  they  contain,  as 
Dr.  Johnson  remarks,  exceedingly  minute  granules,  which  are 


128 


THE  URINE  IN  HEALTH  AND  DISEASE. 


incessantly  dancing  about  with  so-called  1  Brownian  movement.' 
The  same  authority  states  that  '  there  is  no  known  substance 
occurring  in  either  normal  or  abnormal  urine,  except  albumen, 
which  gives  a  precipitate  with  picric  acid  insoluble  by  the  subse- 
quent application  of  heat.  This  is  incorrect.  Urine  containing 
semen  gives  a  precipitate  with  picric  acid  solution  practically 
unaffected  by  heat.  While  the  fluid  is  still  warm  the  addition 
of  a  little  nitric  acid  renders  it  quite  transparent,  and  the 
transparency  is  permanent.  If  to  the  same  urine  before  boiling 
nitric  acid  be  added,  after  the  precipitation  by  picric  solution, 
the  precipitate  is  dissolved,  and  the  fluid  becomes  transparent, 
but  the  transparency  soon  passes  off.' 

Uric  acid  is  precipitated  from  normal  urine  by  picric  acid.*  I 
have  observed  that  the  precipitate  is  very  like  albumen  in 
appearance,  and  disappears  on  boiling,  the  fluid  assuming  a 
beautiful  pink  colour.  This  applies  to  urine  containing  potash 
in  excess.  In  the  case  of  urine  containing  an  excess  of  urate  of 
ammonia,  the  addition  of  picric  acid,  and  exposure  to  air  for  a 
little  time,  causes  the  urine  to  assume  a  deep  port- wine  colour, 
but  in  my  experience  no  precipitate.  The  deposit  most  readily 
and  abundantly  forms  when  the  acid  is  employed  in  the  form  of 
fine  powder,  instead  of  the  aqueous  solution.  Under  the  micro- 
scope the  deposit  appears  as  fine,  needle-like  processes,  in  the 
form  of  stars,  and  of  more  or  less  irregular  prismatic  crystals. 
Acted  on  by  boiling  water,  part  of  the  precipitate  forms  a  com- 
bination of  creatinine  with  pier  ate  of  potassium. 

In  using  the  aceto-picric  test,  or  Tanret's  solution  and  heat, 
according  as  the  urine  is  rich  in  albumen,  it  appears  in  two 
forms.  When  but  a  small  quantity  of  albumen  is  present,  a 
mere  cloud  is  produced,  and  this  Professor  Bouchard  has  proposed 
to  term  the  non-retractile  form  of  albumen.  When  present  in 
larger  quantity,  distinct  flakes  are  formed,  termed  by  the  same 
authority  the  retractile  form. 

Dr.  Dickinson  considers  the  picric  acid  and  the  mercuric 
iodide  tests  as  not  sufficiently  discriminating. 

Ferrocyanide  of  Potassium  Test.— A  solution  of  ferrocyanide 
of  potassium  acidulated  with  acetic  acid  forms  a  delicate  test  for 

*  Zeit.fur  Physiol.  Chem.,  1886,  p.  39. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  129 


albumen.  A  preliminary  objection  to  the  use  of  all  tests  requiring 
acidulation  by  acetic,  citric,  or  lactic  acid  is,  that  by  either  of 
these  mucin  is  thrown  down,  and  such  acidulated  tests  are 
unsuitable  for  urines  containing  a  small  quantity  of  albumen. 
For  ordinary  purposes  in  practice,  Dr.  Pavy  has  suggested  a 
most  convenient  contrivance  for  the  application  of  this  test ; 
pellets  containing  a  sufficient  quantity  of  citric  acid  and  ferro- 
cyanide of  potassium  being  formed  and  enclosed  in  an  indiarubber 
capsule.*  These  are  carried  about  in  a  small  tube,  and  as  no 
heat  is  required  in  testing  with  them,  they  are  of  easy  appli- 
cation. Dr.  Pavy's  directions  are  as  follows  :  About  a  drachm  of 
urine  is  taken,  an  acid  pellet  is  dropped  into  it,  which  a  little 
agitation  quickly  dissolves.  One  of  the  ferrocyanide  pellets  is 
next  dropped  in,  and  the  urine  again  shaken  to  facilitate  solution. 
If  albumen  be  present,  a  precipitate  immediately  occurs.  Should 
the  urine  contain  urates,  it  is  to  be  clarified  by  heating.  On  the 
addition  of  the  acid  pellet  alone  a  precipitate  is  sometimes  formed, 
and  this  precipitate  may  be  due  either  to  mucin  or  to  uric  acid. 
In  the  latter  case,  dilution  of  the  urine  with  an  equal  bulk  of 
water  prevents  the  appearance  of  the  precipitate ;  in  the  former 
case,  the  precipitate  with  both  the  acid  and  the  ferrocyanide 
pellet  should  be  compared  with  that  resulting  from  the  acii 
alone. 

A  concentrated  solution  of  ferrocyanide  of  potassium  with 
acetic  acid  is,  according  to  Hofmeister,  the  most  delicate  of  all 
the  albumen  tests,  and  it  precipitates  all  the  albuminous  bodies, 
but  not  peptones.  Salkowski  states  that  this  test  fails  when  a 
large  amount  of  chloride  of  sodium  is  present,  but  the  urine 
never  contains  this  element  in  such  quantity  as  to  prevent  the 
precipitation  of  albumen. 

Dr.  Zouchlos  recommends  the  following  as  convenient  bedside 
tests  for  albumen  in  the  urine :  1.  Some  drops  of  a  mixture  of  1 
part  of  acetic  acid  and  6  parts  of  a  1  per  cent,  solution  of  subli- 
mate, when  added  to  urine  containing  albumen,  produce  a  slight 
cloudiness.  Peptone,  when  mixed  with  acetic  acid  and  sublimate 
in  the  above-mentioned  proportions,  causes  no  cloudiness,  and 

*  These  pellets  may  be  obtained  from  Mr.  Cooper,  66,  Oxford 
.Street,  London. 

9 


130 


THE  UBINE  IN  HEALTH  AND  DISEASE. 


this  is  true  also  of  uric  acid,  solution  of  urea,  phosphates  and 
sugar.  When  the  urine  is  much  concentrated,  it  does  not  be- 
come cloudy  on  the  addition  of  sublimate  and  acetic  acid. 
2.  Another  method  which  is  still  more  exact — even  more  so  than 
that  with  the  ferrocyanide  of  potassium  and  acetic  acid — is  the 
method  with  rhodanide  of  potassium  and  acetic  acid  in  the  cold. 
It  is  best  to  mix  100  c.c.  of  a  10  per  cent,  solution  with  20  c.c. 
of  acetic  acid,  and  to  add  some  drops  of  this  mixture  to  the  urine 
to  be  tested.  When  albumen  is  present  in  small  quantities,  a 
distinct  cloudiness  occurs  immediately  on  the  addition  of  the 
above-mentioned  mixture  ;  when  the  amount  of  albumen  is  large, 
a  thick  white  precipitate  is  thrown  down.  An  excess  of  the  fluid 
does  no  harm.  Normal  urine,  when  thus  tested,  invariably  gives 
a  negative  result.  The  most  convenient  method  is  that  with 
rhodanide  of  potassium  and  succinic  acid,  which  can  be  carried 
about  in  the  solid  form  in  boxes.  Equal  parts  of  succinic  acid 
and  rhodanide  of  potassium  are  mixed  together,  and  a  small 
quantity  is  added  to  the  urine.  If  even  the  smallest  amount  of 
albumen  is  present,  cloudiness  is  produced. 

Nitroprussiate  of  Soda  Test. — M.  G.  Nya*  recommends  a 
solution  of  nitroprussiate  of  soda  as  a  test  for  albumen.  It  is 
to  be  employed  in  the  same  manner  as  ferrocyanide  of  potassium  ; 
that  is  to  say,  before  a  solution  of  the  reagent  is  added  to  the 
suspected  urine,  it  must  be  previously  acidulated  by  acetic  acid. 
When  precipitation  of  urates  occurs,  the  urine  must  be  clarified 
by  heating.  The  nitroprussiate  solution  must  be  protected  from 
light  in  order  to  prevent  decomposition. 

Sodium  Tungstate  Test. — We  are  indebted  to  F.  L.  Sonnen- 
scheinf  for  the  recommendation  of  sodium  tungstate  as  an 
albumen  test. J  The  solution  of  this  salt  must  be  acidulated 
with  acetic  or  phosphoric  acid.  It  precipitates  peptones,  acid 
urates,  and  mucin.  In  combination  with  strong  acetic  acid, 
sodium  tungstate  is  a  more  delicate  albumen  test  than  with 
citric  acid.    With  the  latter  it  gives  a  marked  mucin  reaction. 

*  Med.  Chir.  Rundschau,  1887,  and  Archiv  de.r  Pharm.  xxv.,  1887. 
t  Journal  of  the  Chemical  Society,  March,  1874. 
%  Also  as  a  delicate  test  for  blood,  producing,  with  ammonia,  a  green 
colour  when  blood  is  so  diluted  as  not  to  be  recognisable  by  the 

spectroscope. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  131 

Spiegler's  Test.* — According  to  Spiegler,  the  following  reaction 
discovers  albumen  when  it  exists  in  the  urine  in  so  small  a  pro- 
portion as  1  part  in  250,000  :  Corrosive  sublimate  8  parts,  tartaric 
acid  4  parts,  distilled  water  200  parts,  glycerine  20  parts.  A 
test-tube  is  filled  to  a  third  of  its  capacity  with  the  reagent,  to 
which  a  few  drops  of  acetic  acid  have  been  added,  by  pouring 
along  the  tube  wall,  and  the  urine  carefully  added.  When 
albumen  exists,  an  opaque  ring  forms  at  the  junction  of  the 
fluids.  Should  the  urine  at  the  same  time  contain  iodine,  the 
albuminous  ring  becomes  of  a  yellow  colour,  the  iodine  yellow 
dissolving  in  alcohol.  The  added  acetic  acid  separates  almost 
all  the  mucin.  With  this  reagent,  Spiegler  has  been  able  to 
detect  transitory  albuminuria  in  from  twelve  to  twenty-four 
hours  after  physical  or  intellectual  exertion. 

Stutz's  Test. — This  consists  of  a  mixture  of  bichloride  of 
mercury,  chloride  of  sodium,  and  citric  acid.  Added  to  albu- 
minous urine,  this  solution  causes  an  abundant  precipitate  of 
albuminate  of  mercury.  It  is  to  be  noted  that  it  likewise 
precipitates  uric  acid  in  urines  rich  in  this  acid,  and,  therefore, 
in  employing  the  test,  the  urine  should  be  diluted  with  an  equal 
quantity  of  water. 

Jaworowski  (Wiadomosci  Farmacentyezne,  June,  1892)  sug- 
gests, as  a  most  delicate  test  for  albumen,  1  part  of  molybdate 
of  ammonia  with  40  parts  of  water  and  5  parts  of  tartaric  acid. 
The  presence  of  ^ooVoo  °^  albumen  is  thus  revealed.  The 
urine  must  be  limpid  and  acid.  If  necessary,  it  may  be  acidified 
with  tartaric  acid.  The  albumen  may  be  completely  removed 
by  gradual  addition  of  the  reagent  and  filtration.  An  excess 
dissolves  the  albumen. 

Koch's  Test— Sulphosalicylic  Acid.— This  acid,  which  is 
obtained  by  the  action  of  sulphuric  acid  on  salicylic  acid,  has 
been  recommended  as  a  most  sensitive  albumen  test  by  M. 
Roch.  When  the  acid  is  added  to  an  albuminous  solution,  a 
white  precipitate  possessing  an  acid  reaction  results,  which,  on 
being  treated  with  perchloride  of  iron,  gives  an  intense  red 
coloration  characteristic  of  sulphosalicylic  acid.   The  compound 

*  '  Uber  eine  empfindliche  Reaktion  auf  Eiweiss  im  Harn,'  etc. 
(Centralblatt  f.  Klin.  Medic,  1893,  No.  3,  p.  49). 


132 


THE  URINE  IN  HEALTH  AND  DISEASE. 


thus  formed  with  albumen  is  insoluble,  and  resembles  that 
obtained  with  metaphosphoric  acid.  The  whole  of  the  albumen 
is  precipitated,  and  0*0005  gramme  of  albumen  may  be  thus 
detected  in  10  c.c.  of  albuminous  urine.  In  employing  the  test 
a  few  crystals  of  sulphosalicylic  acid  are  to  be  added  to  a  small 
quantity  of  urine  and  the  fluid  shaken.  The  presence  of  albumen 
is  revealed  as  above.  The  reaction  is  not  interfered  with  by  the 
presence  of  urea,  uric  acid,  peptones,  sugar  or  other  substances. 
(ArcJiiv  der  Pharmacie,  xxvii.,  1889,  998;  and  L'Orose,  xi., 
December,  1889,  413.) 

Other  Tests  for  Albumen.— Of  the  other  tests  for  albumen 
may  be  mentioned  acidulated  br  ine,  first  suggested  by  Sir  "William 
Koberts,  and  since  abandoned  by  him ;  alcohol,  which,  while  it 
precipitates  albumen,  also  coagulates  mucus,  and  renders  certain 
salts  insoluble  ;  tannin,  which  also  precipitates  mucus,  and  other 
animal  substances  which  the  urine  contains ;  alum,  which  deter- 
mines precipitates  in  urine  not  albuminous  ;  corrosive  sublimate, 
which  seldom  fails  to  precipitate  urine  whether  it  contains 
albumen  or  not,  being  decomposed  by  the  sulphates,  phosphates, 
and  the  organic  matter  in  the  urine  ;  carbolic  acid,  and  Tidy's 
test,  which  consists  of  equal  parts  of  carbolic  and  acetic  acids,  and 
acetate  of  uranium ;  acetic  acid,  with  sulphate  or  chloride 
of  sodium  (Panum,  Heynsius) ;  trichloracetic  acid  (Raabe)  ; 
Millon's  reagent ;  biuret  reaction ;  reaction  of  Adamldevicz. 
Urine  containing  albumen,  on  being  shaken,  retains  its  froth  for 
an  indefinite  period,  sometimes  for  days.  These  tests  are  much 
less  trustworthy  than  those  described  in  detail,  and  do  not  merit 
further  consideration.* 

Mixed  Albuminuria. — Blood  normally  contains  two  coagu- 
lable  albuminous  substances,  viz. :  serum-albumen  (serine)  and 
globulin.  In  the  majority  of  instances  in  which  serum-albumen 
is  found  in  the  urine,  globulin  coexists  with  it.  In  a  small 
number  of  instances,  it  sometimes  happens  that  but  one  of  these 
constituents  is  found,  and  thus  we  may  have  a  pure  case  of 
serinuria  or  globinuria.   Globulin  is  a  more  diffusible  substance 

*  Dr.  Oliver,  of  Harrogate,  has  applied  most  of  these  tests  to 
clinical  purposes  in  the  form  of  test-papers,  after  the  manner  first 
suggested  by  Professor  de  Luna,  of  Madrid  {Lancet,  October  14,  1882). 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  133 


than  serum -albumen,  and  when  but  one  of  these  bodies  exists, 
it  is  more  likely  to  be  globulin.  When  albumen  reaches  the 
stomach  it  is  coagulated,  and  in  this  form  insoluble  in  water. 
Here  it  is  acted  upon  by  the  gastric  juice,  dissolved,  and  con- 
verted into  peptone,  though  in  this  condition  but  slight  traces  of 
it  are  found  in  the  blood ;  yet,  as  with  urea,  uric  acid,  and  kreatin, 
the  kidney  separates  it  from  the  blood,  and  it  may  exist  in  large 
quantity  in  the  urine,  constituting  peptonuria.  The  conversion 
of  albumen  into  peptone  is  by  successive  stages,  and  hence  inter- 
mediate products  may  find  their  way  into  the  blood,  and  ultimately 
into  the  urine.  The  most  important  of  these  compounds  is  hemi- 
albumose,  or  propeptone.  According  to  Senator,  the  occurrence 
of  propeptone  in  the  urine  is  by  no  means  a  rare  occurrence. 
Cases  occasionally  occur  in  which  propeptone,  serum-albumen, 
and  globulin  occur  simultaneously  in  the  urine,  and  to  such  the 
term  *  mixed  albuminuria  '  specially  applies. 

Globulin  is  precipitated  by  sulphate  of  magnesia  ;  propeptone 
is  not  precipitated  from  its  watery  solution  by  boiling,  but  is 
precipitated  in  the  cold  state  by  acetic  acid,  and  ferrocyanide  of 
potassium,  nitric  acid,  acetic  acid,  and  a  concentrated  solution 
of  chloride  of  sodium.  Peptones  are  not  precipitated  by  heat, 
nitric  acid,  nor  the  ferrocyanide  test,  but  are  precipitated  by 
picric  acid,  the  precipitate  disappearing  on  the  application  of 
heat,  to  reappear  on  cooling,  and  by  the  mercuric-iodide  and 
tungstate  tests,  the  precipitant  similarly  disappearing  and  re- 
appearing. Fehling's  solution,  it  may  here  be  remarked,  though 
in  anticipation,  gives  a  characteristic  rose  or  pink-tinted  colour 
with  peptones. 

In  all  cases  in  which  there  is  doubt  as  to  the  presence  of  pro- 
peptone, peptones,  and  albumen  existing  simultaneously  in  the 
urine,  the  following  procedure  should  be  adopted :  (1)  Acidify 
the  urine  with  acetic  acid,  and  then  carefully  add  a  concentrated 
solution  of  ferrocyanide  of  potassium.  All  the  albuminous 
bodies  are  thus  precipitated,  but  not  peptones.  (2)  Add  care- 
fully a  little  nitric  acid  to  the  non- warmed  urine,  and  if  cloudi- 
ness result,  boil  the  urine.  If  the  precipitate  then  partially 
or  entirely  disappear,  the  presence  of  propeptone  is  indicated. 
(3)  A  concentrated  solution  of  chloride  of  sodium  or  sulphate  of 


134 


THE   URINE  IN  HEALTH  AND  DISEASE. 


magnesia  added  to  urine  acidulated  with  acetic  acid  or  nitric 
acid  gives  a  precipitate  which  disappears  on  heating;  then  prc- 
peptone  is  likewise  indicated.  Mucin  is  precipitated  b}T  citric  or 
acetic  acid,  and  may  be  removed  by  nitration. 

Hindenlang*  recommends  metaphosphoric  acid  as  a  delicate 
test  for  albumen,  but  it  likewise  precipitates  peptones.  A  pre- 
cipitate caused  by  this  acid,  but  not  by  acetic  acid  and  ferro- 
cyanide  solution,  in  the  original  urine,  would  indicate  peptone 
to  the  exclusion  of  other  substances.  Should  the  urine  give  a 
precipitate  with  these  two  reagents,  then  by  boiling  and  filtering 
the  serum-albumen  and  globulin  may  be  separated.  The  filtrate 
should  not  give  a  precipitate  with  acetic  acid  and  ferrocyanide  of 
potassium  ;  but  if  peptone  be  present,  a  precipitate  would  be 
given  with  metaphosphoric  acid. 

Kelative  Value  and  Delicacy  of  the  Various  Albumen 
Tests. — In  view  of  the  pathological  importance  which  attaches 
to  the  early  detection  of  albumen  in  the  urine,  and  the  vast 
number  of  details  which  fall  to  be,  or  are  supposed  to  be,  re- 
membered by  the  student,  it  is  not  desirable  that  equivocal 
albumen  tests  should  be  indefinitely  multiplied,  but  rather,  from 
the  practical  point  of  view,  that  the  relative  delicacy  and  conse- 
quent value  of  the  best  known  of  them  should  be  determined. 
The  following  table  exhibits  the  result  of  careful  experiments 
undertaken  by  rue  for  this  purpose. 

*  Berlin  Klinik  Wochenschrift,  1881,  No.  15. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  135 


Solution  of 
sodium  tungstate 
with  citric  acid. 

Well-markea 
instantaneous 
albumen  preci- 
pitate. 

Distinct  alDU- 
men  reaction ; 
precipitate 
floating. 

Appreciable  pre- 
cipitate. Not 
nearly  so  dis- 
tinct as  in  com- 
bination with 
acetic  acid. 

AppreciaDie 
precipitate. 

No  reliable 
precipitate. 

Solution  of 
sodium  tung- 
state with 
acetic  acid. 

Copious 
and  well- 
marked 
albumen 
precipitate. 

Well- 
marked 
albumen 
precipitate, 
clear  super- 
natant disc. 

Distinct 
precipitate 

against 
clear  super- 
natant disc. 

Distinct 
precipitate 

against 
supernatant 
fluid. 

No  reliable 
precipitate. 

S  5  5;  !3 
e 

JrJf 

Distinct 
supernatant 

albumen 
precipitate, 
semi-trans- 
parent. 

Albumen 
precipitate  ; 
more  trans- 
parent, 
milky. 

No  appre- 
ciable 
result. 

No  result. 

1 

1 

Coagulation 
by  heat. 

Well-marked 
albumen  pre- 
cipitate at 
boiling 
point. 

Distinct  albu- 
men precipi- 
tate at  boiling 
point ;  less 
opaque. 

Distinct  pre- 
cipitate at 
boiling  point  ; 
less  copious. 

Appreciable 
precipitate  at 
boiling  point. 

Appreciable 
albumen  reac- 
tion at  boiling 
point. 

Albumen  re- 
action at 
boiling  point. 

Albumen  re- 
action at 
boiling  point. 

Faintest  pos- 
sible reaction 
at  boiling- 
point. 

Nitric  acid, 
Heller  s 
method.  j 

Well-marked 
albumen  pre- 
cipitate ;  floc- 
culent and 
settling  on 
repose. 

Well-marked 
albumen  reac- 
tion ;  more 
distinct  on 
repose. 

Distinct  pre- 
cipitate ;  more 
mai'ked  on 
repose. 

Distinct  pre- 
cipitate, but 
only  after  an 
interval  of 
10  minutes. 

Distinct  albu- 
men reaction 

after  an  in- 
terval of 

15  minutes. 

Albumen  re- 
action after 
15  minutes. 

Faint  albu- 
men reaction 
after  1  hour. 

No  reliable 
result. 

Saturated  solu- 
tion of  -picric 
acid  vnth  citric 
acid. 

An  abundant 
albumen  preci- 
pitate of  yellow- 
ish colour,  occu- 
pying greater 
part  of  tube. 

Well-marked 
floating  yellow- 
ish precipitate. 

Well-marked 
floating  yellow- 
ish precipitate, 
less  dense. 

Distinct  super- 
natant yellow 
precipitate,  t 

Very  faint 
yellowish  pre- 
cipitate. X 

Albumen 
reaction.  § 

No  appreciable 
reaction. 

1 

Saturated  solu- 
tion of  picric 
acid. 

A  distinct 
opaque  yellow- 
ish precipitate 
floating  on  the 
clear  fluid 
underneath. 

Distinctly 
marked  albu- 
men reaction  ; 
yellowish 
supernatant 
precipitate. 

Yellowish 
supernatant 
albumen  ;  pre- 
cipitate more 
transparent. 

Marked  yellow 
albumen 
reaction. 

Very  faint 
yellowish  preci- 
pitate. 

Albumen  reac- 
tion slight. 

No  appreciable 
reaction. 

1 

Tanret' 8  solu- 
tion with  heat. 

A  distinct 
precipitate, 

which  settles 
and  becomes 

flocculent  on 
repose. 

Marked  albu- 
men reaction  ; 

precipitate 
flocculent  and 
separating  on 
repose. 

Marked  albu- 
men reaction 
at  boiling 
point. 

Distinct  albu- 
men reaction 
at  boiling 
point. 

Distinct  albu- 
men reaction 

at  boiling 
point.  More 
distinct  than 
'Tanret'  alone. 

Appreciable 
albumen 
reaction. 

Albamen  reac- 
tion, but  less 
marked  than 
by  No.  1. 

process. 

Negative 
result. 

Tanret's  solu- 
tion, the  urine 
poured  drop  by 
drov  on  it. 

A  distinct 
opaque  disc  of 
albumen  float- 
ing m  a  milky 
fluid. 

Distinct  su- 
pernatant al- 
bumen preci- 
pitate, less 
opaque  and 
more  diffused. 

Distinct  albu- 
men precipi- 
tate, less 
opaque  and 
less  copious. 

A  delicate 
supernatant 
precipitate. 

Immediate 
but  faint  pre- 
cipitate. 

Supernatant 
pale  albumi- 
nous disc. 

Faint  super- 
natant albu- 
men reaction. 

Exceedingly 
faint  albumen 
reaction.  Fur- 
ther dilution 
negative. 

Quantity  of 
albumen  in 
1,000  grms. 

& 
o 

o 

3D 
iO 

© 

u 

bo 

iO 

7* 

CN 

b 

& 
to 
p 
b 

h 

bo 
eo 
o 
b 

0-015  gr. 

o 
p 
b 

0-0035  gr. 

136  THE  URINE  IN  HEALTH  AND  DISEASE. 


The  conclusions  which  these  experiments  impress  upon  me 
are :  That  the  delicacy  of  the  best  albumen  tests  stands  in  the 
following  order  :  Tanret's  solution  (open  to  the  objections  men- 
tioned above),  heat,  nitric  acid,  and  aceto-picric  solution. 

The  foregoing  table  further  shows  (a  result  which  is  at  variance 
with  the  statement  of  Hofmeister)  that  ferrocyanide  of  potas- 
sium with  acetic  acid  proved  in  my  hands  the  least  delicate  of 
the  tests  employed,  ceasing  to  give  any  result  with  1  part  in 
8,833  ;  that  tungstate  of  soda  with  citric  acid  is  less  delicate 
than  with  acetic  acid,  the  latter  ceasing  to  give  a  precipitate  at 
1  part  in  33,333 ;  that  the  aceto-picric  solution  ceases  to  give  a 
reaction  at  1  part  in  148,857*5,  but  gives  a  reaction  at  1  part 
in  66,666.  Sir  William  Eoberts  states  that,  in  his  hands,  the 
picric  acid  tests  gave  a  faint  reaction  in  a  watery  solution  con- 
taining 1  part  in  100,000.    I  have  been  unable  to  confirm  this.* 

Quantitative  Analysis. — The  most  accurate,  though  certainly 
the  most  troublesome,  method  of  determining  the  amount  of 
albumen  in  solution  in  any  fluid,  is  that  by  weighing.  For  this 
purpose  coagulation  is  necessary,  and  this  may  be  accomplished 
either  by  boiling  the  urine,  or  by  coagulating  the  albumen  by  a 
chemical  agent,  filtering,  collecting,  and  then  weighing.  If  the 
former  process  be  adopted,  a  certain  quantity  of  urine  is  taken, 

*  With  reference  to  the  heat  test,  Sir  William  Roberts  ('Discussion 
on  Albuminuria'  at  Glasgow  Pathological  and  Clinical  Society,  1884) 
remaiked  :  '  I  gauged  the  delicacy  of  the  test  in  the  following  manner  : 
A  moderately  albuminous  urine  was  diluted  with  2,000  times  its  bulk 
of  water.  I  could  with  certainty  detect  the  presence  of  albumen  in 
this  dilution  by  the  boiling  test.  Now,  the  urine  operated  on  was 
found,  on  a  careful  weighing  analysis,  to  contain  076  per  cent  of  dry 
albumen.  If  you  work  out  the  sum  which  these  figures  furnish,  you 
will  get  the  astonishing  result  that  the  boiling  test,  with  due  acidula- 
tion,  enables  you  to  detect  albumen  in  a  watery  solution  which 
contains  only  one  part  in  250,000.'  Sir  William  Roberts's  calculation 
is  slightly  wrong.    His  data  give  one  part  in  263,158. 

Professor  Grainger  Stewart  {Edin.  Med.  Jour.,  May,  1887)  states 
it  as  his  (  pinion  that  picric  acid  is  the  most  delicate  of  all  the  reagents 
which  we  possess  for  albumen,  the  potassio- mercuric  iodide  ranking 
next  to  it  ;  whiie  Dr.  Unger  Vetlesen,  of  Christiania,  believes  the 
relative  delicacy  to  be  represented  by  the  following  figures  :  Heller's 
test,  85  ;  trichloracetic  acid,  82  ;  ferrocy.  potass,  and  acid,  acet.,  82  ; 
metaphosphoiic  acid,  72;  picric  acid  in  solution,  36  ;  Glauber's  salt 
and  acetic  acid,  25. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  137 


from  50  to  150  grammes  being  a  convenient  amount ;  a  few 
drops  of  acetic  acid  are  added  to  it,  so  as  to  render  it  distinctly 
acid,  and  it  is  then  filtered.  According  as  the  urine  is  rich  in 
albumen,  the  nitration  will  be  slowly  accomplished.  If  rich  in 
albumen,  water  should  be  added,  so  that  from  25  to  100  cubic 
centimetres  of  the  solution  should  contain  from  0*30  gr.  to 
0*50  gr.  of  dried  albumen,  as  judged  by  the  qualitative  analysis. 
The  diluted  urine  is  then  put  into  a  porcelain  capsule,  and 
gradually  heated  to  ebullition,  the  fluid  being  stirred  by  means 
of  a  glass  rod.  The  boiling  should  be  continued  from  a  quarter 
to  half  a  minute,  and  the  fluid  then  passed  through  a  filter, 
whose  weight  has  been  previously  determined.  Filtration  takes 
place  rapidly ;  the  capsule  is  then  washed  with  distilled  water, 
the  adherent  particles  of  the  precipitate  being  detached,  and 
the  fluid  and  the  remaining  precipitate  is  again  thrown  on  the 
filter.  Then,  by  means  of  a  pipette  containing  boiling  distilled 
water,  the  albuminous  precipitate  is  washed,  the  jet  being  directed 
so  as  to  convey  the  albumen  towards  the  cone  of  the  filter. 
The  washing  is  to  be  continued  until  the  albumen  becomes 
perfectly  white.  The  washing  removes  the  chlorides  from  the 
albumen.  Sometimes  it  is  necessary  to  use  hot  alcohol  for  the 
purpose  of  washing.  The  filter  and  contents  are  now  carefully 
placed  in  a  stove,  and  exposed  to  a  temperature  of  100°C.  Desic- 
cation takes  from  five  to  six  hours,  and  the  mass  must  be  so 
arranged  as  to  facilitate  this.  The  desiccation  is  known  to  be 
complete  when  two  weighings  at  an  interval  of  from  half  an  hour 
to  an  hour,  in  the  stove,  give  an  identical  weight.  From  the 
whole  weight  that  of  the  filter  is  to  be  subtracted,  and  the  dif- 
ference represents  the  weight  of  the  albumen. 

Two  sources  of  error  in  this  process  are  to  be  noted.  In  the 
first  place,  the  albumen  which  passes  into  the  urine  is  identical 
with  that  of  the  serum  of  the  blood ;  it  contains  serine  and  dis- 
solved fibrine.  In  the  second  place,  the  albumen  retains  always 
more  or  less  of  the  colouring  matter  of  the  blood,  and  phosphates 
of  lime  and  magnesia,  especially  if  acetic  acid  has  not  been  added. 
To  obviate  the  former  source  of  error,  the  albumen  should  be 
washed  with  alcohol,  and  to  avoid  the  latter,  the  dried  albumen 
should  be  incinerated,  and  the  weight  of  the  ash  deducted.  These 


138 


THE  UEINE  IN  HEALTH  AND  DISEASE. 


sources  of  error  are,  however,  so  insignificant  as  to  be  clinically 
unimportant. 

Coagulation  of  Albumen  by  Carbolic  Acid  — Process  of 
M^hu. — To  the  albuminous  urine  two  or  three  drops  of  acetic 
acid  are  to  be  added,  and  the  fluid  filtered ;  100  c.c.  of  the 
filtrate  are  then  taken,  and  2  c.c.  of  ordinary  nitric  acid  are 
added,  with  10  c.c.  of  the  following  solution : 

Crystallized  carbolic  acid  ...       ...    10  grammes 

Commercial  acetic  acid  ...       ...       ...    10  ,, 

Alcohol  (90°C.)   20 

The  mixture  being  shaken,  the  albumen  immediately  coagulates, 
and  the  whole  is  thrown  on  a  filter.  Filtration  takes  place  so 
rapidly  that  the  uric  acid  is  almost  entirely  found  in  the  filtered 
fluid,  where  it  gradually  crystallizes.  The  albumen  collected  on 
the  filter  is  washed  with  boiling  water  containing  1  per  cent, 
of  carbolic  acid,  and  is  then  dried  towards  a  temperature  of 
105°  F.  or  C. ;  any  excess  of  carbolic  acid,  being  volatile,  disappears 
with  the  water. 

If  the  urine  be  rich  in  albumen,  a  preliminary  experiment  is 
made  with  from  25  to  30  c.c.  It  should  be  diluted  with  water, 
so  that  the  volume  will  amount  to  100  c.c. 

This  process  is  not  affected  by  the  presence  of  sugar  or  such 
mineral  substances  as  chloride  of  sodium,  nitrate  of  potash, 
iodide  of  potassium,  sulphate  of  magnesia,  and  ammoniacal 
carbonates.  When  the  urine  contains  carbonate  of  ammonia, 
the  precipitate  has  a  creamy  appearance. 

Process  of  Tanret  and  Troyes.— Tanret  and  Troyes  have 
recommended,  for  the  volumetric  estimation  of  albumen,  its  pre- 
cipitation by  a  double  iodide  of  mercury  and  potassium.  For  the 
precipitating  solution  the  formula  is :  Potass,  iodide  3  22  grammes, 
hydrarg.  bichlor.  1*35  gramme,  aq.  destillat.  ad  100  c.c.  For 
the  confirmatory  solution  :  Hydrarg.  bichlor.  1  gramme,  aq.  destill. 
ad  100  c.c.  One  drop  of  the  precipitating  solution  given  by  a 
pipette  of  the  above  size  precipitates  0*005  gramme  of  albumen, 
so  that  so  many  drops  as  it  takes  to  precipitate  all  the  albumen, 
so  many  times  0*005  gramme  of  albumen  must  have  been  in 
the  solution.    To  save  trouble  in  calculation,  the  same  quantity 


ABNOKMAL  CONSTITUENTS  OF  THE   URINE.  139 


of  urine  should  always  be  taken,  and  the  most  convenient  quantity 
to  take  is  10  c.c,  as  then  the  number  of  drops  of  the  solution 
that  it  takes  to  precipitate  all  the  albumen  in  this  quantity  of 
urine  represents  so  many  half -grammes  to  the  litre.  *  Take 
then  10  c.c.  of  urine,  add  2  c.c.  of  acetic  acid,  and  stir  with 
a  glass  rod ;  add  the  precipitating  solution  drop  by  drop, 
stirring  carefully  each  time,  until  the  precipitate  is  no  longer 
redissolved  in  the  albumen  in  excess,  i.e.,  as  yet  unaffected  by  the 
reagent ;  after  adding  each  drop  of  the  solution,  put  a  drop  of  the 
Urine  on  a  porcelain  dish  and  watch  if  a  yellowish-red  colour 
appears  on  adding  a  minute  drop  of  the  confirmatory  solution. 
As  soon  as  it  does,  all  the  albumen  is  precipitated  and  the  process 
is  finished,  and  the  amount  of  albumen  per  litre  will  be  at  once 
arrived  at  by  taking  the  number  of  drops  employed  of  the  pre- 
cipitating solution,  subtracting  three  as  having  been  used  in 
excess  to  make  the  yellow  colour  perfectly  apparent,  and  then 
considering  the  rest  as  so  many  half-grammes.  The  chemical 
reactions  and  data  on  which  the  above  depends  are  4KI  +  HgCl2 
=  HgI2,2KI-f  2KC1.  When  the  double  iodide  of  mercury  and 
potassium  thus  formed  is  added  to  albuminous  urine  sufficiently 
acidified,  all  the  albumen  is  precipitated  in  combination  with  the 
mercury  and  iodide  of  the  reagent  in  the  proportion  of  the  equi- 
valent of  HgI,KI  (-=^HgI2,2KI)  weighing  393,  to  one  equivalent 
of  albumen  C36H56N90iiS  weighing  1004,  while  the  potassium 
is  taken  up  by  the  acid  of  the  urine.  As  long  as  any  albumen 
remains  in  solution,  the  double  iodide  of  mercury  and  potassium 
will  not  form  red  iodide  of  mercury  when  bichloride  of  mercury 
is  added  to  it,  but  it  does  so  as  soon  as  all  the  albumen  is  preci- 
pitated. The  solution  formulated  above  is  such  that  every  drop 
of  0*05  gramme  contains  0*00196  gramme  of  HgI,KI,  and  there- 
fore, in  accordance  with  the  equivalents  given,  will  precipitate 
•005  of  albumen,  f 
Bodeker's  Method. — Identical  in  principle  with  the  fore- 

*  Supposing  it  takes  10  drops  of  the  precipitating  solution  to 
precipitate  the  albumen  in  10  c.c.  of  urine,  then  0*005  x  10  =*05 
gramme  of  albumen,  and  10  drops  —  10  half-grammes  to  the  litre  ; 
for  10  :  1,000  ::  *05  :  5. 

t  393  :  -00196  ::  1004  :  0*005. 


140 


THE  URINE  IN  HEALTH  AND  DISEASE. 


going  process  is  that  recommended  by  Bodeker.  It  is  based 
upon  the  fact  that  potassic  ferrocyanide  completely  precipi- 
tates albumen  from  an  acid  solution  in  the  proportion  of  211 
ferrocyanide  to  1612  albumen.  The  standard  solution  of 
ferrocyanide  is  made  by  dissolving  1*309  gramme  of  the  pure 
salt  in  a  litre  of  distilled  water.  One  cubic  centimetre  of 
the  solution  thus  prepared  precipitates  0*01  gramme  of  albu- 
men.* 

Analytical  Process. — Take  50  c.c.  of  the  clear  filtered  urine, 
and  mix  with  50  c.c.  of  commercial  acetic  acid,  and  put  the  fluid 
into  a  burette.  Five  filters  are  then  put  into  a  corresponding 
number  of  funnels,  a  few  drops  of  acetic  acid  being  added,  and 
filled  up  with  boiling  water.  In  this  manner  filtration  takes 
place  more  rapidly.  Ten  c.c.  of  the  ferrocyanide  solution  are 
then  measured  into  a  beaker  with  10  c.c.  of  the  ordinary  fluid 
from  the  burette.  The  fluid  is  then  shaken  and  poured  upon 
No.  1  filter.  If  the  fluid  which  passes  through  is  bright  and 
clear  and  of  a  yellowish  colour,  then  the  ferrocyanide  will  be  in 
excess,  and  a  drop  of  the  urine  added  to  it  will  produce  a  cloudi- 
ness. Otherwise,  if  not  enough  of  the  ferrocyanide  has  been 
added,  the  filtrate  will  be  turbid,  and  pass  slowly  through.  Fre- 
quently, in  this  case,  both  the  ferrocyanide  and  the  urine  will 
produce  a  turbidity  when  added.  The  addition  of  too  much 
urine  in  testing  the  filtrate  for  excess  of  ferrocyanide  must  be 
avoided,  so  that  the  precipitate  of  hydro-ferrocyanide  of  albumen 
may  not  be  dissolved  in  the  excess  of  albumen. 

According  to  the  result  obtained  from  the  first  filter,  a  second 
trial  is  made,  increasing  the  quantity  of  urine  or  ferrocyanide 
half,  or  so,  as  much  again,  and  so  on  until  it  is  found  that  the 
solution  first  shown  to  be  in  excess  is  reversed.  The  mean  is 
now  taken  between  this  quantity  and  the  previous  one,  and  the 
final  test  applied. f 

Example. — Fifty  c.c.  of  urine  containing  albumen  were  mixed 
with  a  like  quantity  of  acetic  acid  and  tested  as  follows  : 

*  211  :  1  ::  1612  :  7'6,  and  1  :  1309  ::  7 '6  :  0*0099. 
f  Sutton's  'Volumetric  Analysis.' 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  141 


Urine. 


Ferrocyanide.      Tn  filtrate 
urine  gave 


In  filtrate  ferrocy- 
anide gave 
precip. 
0 

precip. 
faint  precip. 
0 


(1)  10  c.c. 

(2)  10  c.c. 

(3)  10  c.c. 

(4)  10  c.c. 

(5)  10  c.c. 


15  c.c.  0 
17*5  c.c.  0 
18  c.c.  0 


20  c.c.  precip. 


10  c.c.  0 


Hence  10  c.c.  of  the  diluted  urine=5  c.c.  of  the  original  secre- 
tion, contained  0*18  gramme  albumen,  or  36  parts  per  1,000. 
This  process  is  obviously  more  complicated  and  tedious  than 
that  of  Tanret  and  Troyes,  and  possesses  no  superior  advantages 
to  commend  it. 

Process  of  Brandberg. — This  process  consists  in  an  applica- 
tion of  Heller's  method,  and  is  based  on  the  time  necessary  for 
the  appearance  of  the  albuminous  principle  in  certain  dilutions. 
According  to  Brandberg,  Heller's  reaction  appears  as  follows  : 

(a)  Immediately,  in  a  solution  of  one  part  of  albumen  in 
10,000  of  water  (0*01  per  cent.). 

(b)  In  from  quarter  to  half  a  minute,  in  a  solution  of  1  in 
20,000  (0-005  per  cent.). 

(c)  In  about  one  minute  and  a  half,  in  a  solution  of  1  in  25,000 
(0*004  per  cent.). 

(d)  In  from  two  and  a  half  to  three  minutes,  in  a  solution  of 
1  in  30,000  (0-0033  per  cent.). 

(e)  In  about  four  minutes,  in  a  solution  of  1  in  35,000  (0*0028 
per  cent.). 

Basing  the  following  procedure  on  (d),  the  urine  is  diluted  with 
nine  times  its  volume  of  water  (one-tenth  of  urine),  and  Heller's 
test  is  applied  as  follows :  By  means  of  a  pipette  a  little  nitric 
acid  is  placed  in  a  conical  glass,  and  similarly  the  diluted  urine, 
taking  care  not  to  mix  the  two.  If  after  the  lapse  of  three 
minutes  an  albuminous  ring  does  not  appear  at  the  point  of 
junction  of  the  two  fluids,  it  may  be  concluded  that  the  quantity 
of  albumen  does  not  exceed  0*003  per  cent.,  and  consequently  in 
the  pure  urine  not  more  than  0*03  per  cent.  If,  on  the  contrary, 
the  reaction  is  established  within  three  minutes,  the  urine  must 
be  further  diluted  in  the  following  manner  :  Five  glasses  are 
taken  ;  into  each  glass  are  placed  2  c.c.  of  the  urinary  solution : 


142 


THE  URINE  IN  HEALTH  AND  DISEASE. 


four  c.c.  of  water  are  added  to  the  first,  to  the  second  13,  to  the 
third  28,  to  the  fourth  43,  and  to  the  fifth  58  c.c.  of  water.  To 
each  of  these  solutions  nitric  acid  is  added  with  the  precautions 
necessary  in  Heller's  method.  If  one  of  them  gives  a  reaction 
in  from  two  and  a  half  to  three  minutes,  it  is  concluded  that  in 
that  one  the  proportion  of  albumen  is  1  in  30,000  or  0*0033  per 
cent.  Knowing  the  number  of  cubic  centimetres  of  water  added, 
the  quantity  of  contained  albumen  may  be  calculated  by  the 
following  formula  : 

2  x  0-1  x  x  =  (a  +  2)  x  0-0033,* 

in  which  a  represents  the  number  of  c.c.  of  added  water.  The 
following  table  exhibits  the  proportion  of  albumen  per  cent., 
the  number  of  c.c.  of  water  added  being  known,  and  Heller's 
reaction  being  obtained  in  three  minutes. 

*  Supposing,  for  example,  8  c.c.  of  water  have  been  added,  then  : 
2  x  0*1  x  x  =  (8  +  2)  x  0*0033. 
2  x  0-1  x  x  =  (10)  x  0  0033. 
2  x  01  x  x  =  -0.33. 
0-2*  =  -033,  and  x  =  '033  -f-  -2  =  0*165. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  143 


0.0.  of  Diluted 
Urine. 

C.C.  of  Water. 

Albumen  per  Cent. 

2+ 

4 

=  0*049 
=  0-099 

2+ 
2+ 
2+ 

8 
10 
13 

=  0-165 
=  0-198 
=  0-247 

2+ 
2+ 
2+ 
2+ 
2+ 

16 
19 

22 
25 
28 

=  0-297 
=  0-346 
=  0-396 
=  0-445 
=  0-495 

2+ 
2+ 
2+ 
2+ 
2+ 

31 
34 
37 
40 
43 

=  0-549 
=  0-594 
=  0-643 
=  0-693 
=  0-742 

2+ 
2+ 
2+ 
2+ 
2+ 

46 
49 
52 

55 
58 

=  0-792 
=  0-841 
=  0-891 
=  0-940 
=  0-990 

2+ 
2-h 
2+ 
2+ 
2+ 
2+ 

61 

64 
67 
70 

73 
88 

=  1-039 
=  1-089 
=  1-138 
=  1-188 
=  1-237 
=  1-485 

Hammerstein  has  made  experiments  with  a  view  to  testing 
the  accuracy  of  the  above,  and  he  has  shown  that  with  a  little 
experience  the  amount  of  variation,  as  tested  by  weighing,  does 
not  exceed  0'05  per  cent. 

Esbach's  Process. — This  method  is  based  on  the  fact  that 
picric  acid  precipitates  albumen  at  the  ordinary  temperature, 
and  that  the  precipitate  deposits  in  a  uniform  state  and  degree 
of  density.  The  apparatus  employed  consists  of  a  tube,  in 
appearance  like  a  large-sized  test-tube,  but  of  greater  thickness,. 


144 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


— R 


and  graduated  so  as  to  indicate  the  amount  of  deposits.  The 
graduation  of  the  instrument  represents  in  grammes  the  quantity 
of  albumen  contained  in  a  litre  of  the  urine  operated 
upon,  the  interspaces  diminishing  towards  the  open 
extremity  of  the  tube,  the  weight  exercised  by  the 
reagent  being  greater  on  the  portion  of  the  deposit 
nearest  it. 

The  Reagent.— Take  10  grammes  of  chemically 
pure  picric  acid,  and  20  grammes  of  citric  acid  dried 
in  the  air.  Dissolve  in  800  or  900  grammes  of 
water,  and,  after  cooling,  add  sufficient  water  to 
obtain  1,000  c.c,  or  1  litre. 

The  albuminous  urine  must  be  acid.  If  not  acid, 
a  few  drops  of  acetic  acid  must  be  added.  The 
urine  is  poured  into  the  albumenimeter  up  to  the 
mark  U,  and  then  the  reagent  is  added  up  to  the 
part  of  the  tube  indicated  by  the  letter  E.  The 
fluids  are  then  mixed  without  violent  agitation,  so 
as  to  prevent  the  formation  of  air-bubbles.  This 
being  accomplished,  the  open  extremity  is  covered 
by  means  of  a  little  gutta-percha  sheeting  or  cork, 
and  the  instrument  allowed  to  remain  undisturbed 
in  a  vertical  position  for  a  period  of  twenty-four 
hours.  At  the  expiry  of  this  time,  the  figure  indicat- 
ing the  height  of  the  deposit  is  noted,  and  shows  in 
grammes  the  amount  of  albumen  contained  in  a 
litre. 

The  instrument  is  not  graduated  bej-ond  7  per 
1,000.     Hence,  when  the  quantity  of  albumen 
exceeds  this  amount,  it  is  necessary  to  dilute  the 
urine,  the  result  being  multiplied  by  the  amount  of 
dilution,  double  or  triple,  as  the  case  may  be.  The 
method  is  not  adapted  for  minute  quantities  of  albu- 
men, as  it  does  not  indicate  less  than  0*1  per  cent. 
This  process  is   suitable,  from  its  simplicity,  for  clinical 
purposes ;  and  its  accuracy  is  such  that  Graaf  has  found  that, 
between  the  results  obtained  with  it  and  the  polarimeter,  the 
variation  did  not  exceed  from  0*1  to  0*2  per  cent. 


— U 


J 


Fig.  33.— 
Esbach's 
Albumeni- 
meter. 


ABNORMAL  CONSTITUENTS  •  OF  THE  URINE.  145 

Zohar's  Method. — Zahor*has  devised  the  following  quick  and 
ready  method,  which  gives  results  accurate  to  the  first  decimal 
place.  It  depends  on  the  difference  in  the  specific  gravity  or 
density  brought  about  in  the  urine  by  the  removal  of  the 
albumen. 

The  process,  which  is  a  densimetric  one,  is  as  follows :  A 
preliminary  examination  of  the  filtered  urine  is  made,  in  order 
to  determine  approximately  the  amount  of  dilute  acetic  acid 
necessary  to  precipitate  all  the  albumen  when  boiled.  This  is 
ascertained  by  placing  a  small  quantity  of  urine  in  a  test-tube 
with  acetic  acid  and  boiling.  The  coagulum  is  then  removed 
by  filtration.  The  filtrate  should  yield  no  precipitate  with 
acetic  acid  and  potassium  ferrocyanide.  A  convenient  quantity 
of  the  filtered  urine  is  now  placed  in  a  flask  fitted  with  a  cork, 
acetic  acid  having  been  added,  and  the  flask  is  then  placed  in 
boiling  water  for  ten  or  fifteen  minutes.  This  brings  about  the 
coagulation  of  the  albumen,  wThereupon  the  fluid  is  carefully 
filtered  into  a  flask  fitted  with  a  perforated  cork,  through 
which  a  funnel  is  passed.  The  density  of  the  urine  and  of  the 
filtrate  is  then  determined  by  means  of  a  urinometer,  graduated 
to  the  fourth  decimal  place.  The  difference  between  the  initial 
density  and  the  final  density  is  now  multiplied  by  the  factor 
400,  the  product  giving  the  number  of  grammes  of  albumen 
present  in  100  c.c.  of  the  urine. 

Pathological  Significance. — In  the  condition  of  perfect 
health  albumen  does  not  exist  in  the  urine.  From  this  stand- 
point, then,  when  it  does  so  exist,  it  may  be  viewed  as  invariably 
possessing  a  pathological  significance.  It  does  not,  however, 
follow  that  the  appearance  of  albumen  in  the  urine  is  neces- 
sarily due  to  structural  change  in  the  renal  tissues,  for,  on  the 
one  hand,  albumen  may  exist  in  the  urine  without  any  appre- 
ciable renal  change,  and,  on  the  other,  there  may  be  considerable 
kidney  change  without  the  accompaniment  of  albumen  in  the 
urine.  Two  inferences  seem  to  be  justly  deducible  from  these 
facts :  on  the  one  hand,  conditions  apart  from  the  kidney  may 
occasion  albuminuria ;  and,  on  the  other,  it  is  only  when  special 
portions  of  the  kidney  are  affected  that  albuminuria  results. 
*  Zeitschrift  fur  Physiolog.  Cliem.  (12,  484-489). 

10 


146 


THE  URINE  IN  HEALTH  AND  DISEASE. 


Between  the  blood  and  the  secretory  apparatus  of  the  kidney,  as 
in  the  case  of  all  the  other  secretory  organs  of  the  body,  there  is 
what  may  be  called,  for  want  of  a  better  term,  a  vital  correlation, 
whereby  the  cells  separate  from  the  blood  the  peculiar  and 
special  constituents  of  the  urine.  Why  or  how  the  cells  of  the 
various  secretory  organs  secrete  only  their  own  peculiar  secre- 
tions, to  the  exclusion  of  others,  we  cannot  explain.  We  have 
to  regard  it  simply  as  an  ultimate  fact.  This  correlation,  in  the 
case  of  the  kidne}7,  may  be  deranged  from  two  opposite  direc- 
tions— viz.,  structural  change  of  the  kidney,  unfitting  it  for  its 
work  as  a  depurating  organ,  or  change  in  the  blood  supplied  to 
the  kidney,  poisoning,  so  to  speak,  the  renal  tissues  temporarily, 
or  leading  to  permanent  change.  Further,  given  perfectly 
healthy  blood  and  perfectly  healthy  renal  structure,  the  blood 
must  pass  through  the  gland  at  a  certain  rate  of  circulation  and 
a  certain  degree  of  vascular  tension.  Hence  albuminuria  may 
be  either  of  a  pathological  or  physiological  nature  primarily,  and 
its  varieties  may  be  thus  classified : 


Pathological. 


Physiological. 


Structural  change  Blood  changes, 
of  the  kidnej\ 


Conditions  affecting 
blood  in  the 


the  circulation  of 
kidney. 


Excess  of 
albumen 
in  blood. 


Poisoning  by  phos- 
phorus, arsenic,  mer- 
cury, and  lead  ; 
pneumonia,  typhus, 
jaundice,  scarlet 
fever,  anaemia,  leu- 
kaemia, diphtheria, 
diabetes,  hyperp}7- 
rexia ;  excessive 
alkalinity  of  the 
blood. 


Impressions  on  the 
nerves  supplying 
the  kidney  (splanch- 
nics)  ;  spinal  in- 
jury ;  intestinal  irri- 
tation ;  masturba- 
tion; cutaneous  exci- 
tation (cold  bathing, 
etc.)  ;  asphyxia  ; 
cerebral  exhaustion 
(over  -  study,  etc.)  ; 
menstrual  disorders. 


Diseases  of  the 
heart,  lungs,  liver, 
etc.  ;  atony  of  the 
renal  bloodvessel; 
increased  or  dim- 
inished blood- 
pressure;  tumours 
pressing  on  veins, 
pregnancy,  etc. 


Further  consideration  of  these  various  states  does  not  fall 
within  the  province  of  this  work. 

Therapeutical  Indications. — In  albuminuria  arising  from 
acute  inflammation  of  the  kidney,  as  in  inflammatory  affections 
of  all  complex  organic  structures,  the  great  principle  of  physio- 
logical rest  and  vicarious  action  must  be  kept  in  view.  Con- 
sequently the  skin  and  bowels  must  be  so  acted  upon  as  to  spare 
the  kidney  and  relieve  it  of  as  much  work  as  possible.  Hot 
baths  and  diaphoretics  are  therefore  indicated,  and  such  purga- 


ABNOKMAL  CONSTITUENTS  OF  THE  UBINE.  147 


tives  as  remove  the  watery  portion  of  the  blood  to  the  greatest 
extent,  as  elaterium,  scammony,  etc.  Salines  should  on  no 
account  be  administered,  as  they  are  eliminated  chiefly  by  the 
kidney,  and  it  is  difficult  to  comprehend  on  what  foundation  in 
sense  or  reason  the  indiscriminate  use  of  bitartrate  of  potash  is 
advocated  in  acute  nephritis.  The  same  applies  to  large 
draughts  of  diluents,  which  simply  increase  arterial  tension, 
induce  renal  embarrassment,  and  increased  elimination  of 
albumen.  Small  doses  of  bichloride  of  mercury  with  iodide  of 
potassium  have  proved  of  signal  benefit  in  my  hands. 

Purulent  Albuminous  Urine. — Urine  containing  pus  neces- 
sarily contains  albumen,  so  that  when  microscopic  examination 
reveals  leucocytes  or  blood-corpuscles,  the  presence  of  albumen 
is  to  be  anticipated.  Should  the  leucocytes  be  in  such  quantity 
as  to  obscure  the  detection  of  albumen  by  heat,  the  urine  should 
be  acidulated  with  a  few  drops  of  acetic  acid,  filtered,  and  the 
usual  tests  applied.  If  the  quantity  of  albumen  be  very  minute 
after  the  addition  of  the  acetic  acid,  a  saturated  solution  of 
sulphate  of  soda  should  be  added.  By  this  means  albumen  may 
be  detected  in  the  urine  of  men  suffering  from  gonorrhoea,  or  of 
females  suffering  from  acute  or  chronic  inflammation  of  the 
genital  organs. 

In  the  case  of  purulent  albuminous  urine  the  question  will 
arise,  To  what  extent  is  the  albumen  derived  from  the  pus  alone '? 
or  is  this  superadded  to  from  a  renal  source  ?  The  solution  of 
these  questions  often  rests  on  practical  experience  alone.  The 
albumen  due  to  pus  is  in  relatively  small  proportion.  In  the  case 
of  a  large  quantity  of  pus  with  a  small  quantity  of  albumen,  say 
lper  cent.,  or  a  small  proportion  of  pus  with  a  large  quantity  of 
albumen  (5  per  cent.,  e.g.),  the  proper  conclusion  will  be  at  once 
apparent.  Confirmation  must  be  sought  in  the  presence  in  the 
urine  of  tube-casts,  or  renal  epithelium,  and  in  the  indications 
afforded  by  clinical  symptoms. 

Globuline  (Paraglobuline ;  Fibrinoplastic  Substance). — 
The  albuminous  matter  which  exists  in  the  blood-corpuscles 
has  been  termed  globuline  by  Berzelius.  It  has  been  termed 
caseine  of  serum  by  Panum,  and  paraglobuline  by  Kuhne.  In 
the  urine  globuline  is  most  frequently  found  associated  with  true 

10—2 


148  THE  UEINE  IN  HEALTH  AND  DISEASE. 

albumen  (serine),  but  it  may  exist  in  an  isolated  condition,  con- 
stituting the  condition  known  as  glohinuria.  This  substance 
may  be  conveniently  extracted  from  the  crystalline  lens  of  the 
ox.  The  other  globuline  contained  in  the  blood  plasma  (nbrino- 
plastic  substance)  may  be  found  occasionally  in  the  urine,  but 
the  former  is  the  globuline  especially  eliminated  with  the  urine. 
Urine  containing  globuline  presents  certain  characters  in  common 
with  albuminous  urine.  It  is  coagulated  by  heat,  the  fluid, 
however,  remaining  milky,  and  the  coagulum  does  not  become 
dense  except  in  the  presence  of  a  sufficient  quantity  of  a  neutral 
salt  (chloride  of  sodium  or  sulphate  of  soda).  Globuline  is  in- 
soluble in  water  and  alcohol  and  saturated  solutions  of  neutral 
salts ;  it  is  soluble  in  acetic  acid  and  in  dilute  solutions  of  alkaline 
carbonates  and  phosphates.  In  moderately  concentrated  solutions 
of  neutral  salts  it  deviates  the  plane  of  polarization  to  the  right. 
In  presence  of  mineral  acids  and  metallic  salts  it  gives  the 
reactions  of  albumen.  The  point  of  coagulation  of  albumen  is 
72°C. ;  that  of  globuline  is  about  80°C.  Globuline  is  coagulated 
by  alcohol,  by  nitric  acid,  by  potassium  ferrocyanide  with  acetic 
acid,  and  by  Tanret's  solution  ;  so  that  it  must  be  borne  in  mind 
that  in  albuminous  urine  submitted  to  these  tests  the  globuline, 
if  it  exist,  is  also  precipitated  by  them.  The  differential  features 
of  globuline  as  compared  with  albumen  are  as  follow : 

(1)  Ammonia  and  acetic  acid  separately  employed  do  not 
precipitate  globuline,  but  used  successively  they  cause  a  pre- 
cipitate of  globuline. 

It  is  immaterial  which  is  first  added,  providing  the  latter  be 
added  in  sufficient  quantity  to  neutralize  the  former. 

(2)  A  solution  of  globuline  is  precipitated  by  passing  a  current 
of  carbonic  acid  gas  through  it.  This  precipitate  is  redissolved 
by  passing  a  current  of  air  through  the  solution  in  like  manner 
for  a  sufficient  length  of  time. 

A  concentrated  solution  of  globuline  feebly  acid  or  alkaline  is 
precipitated  by  chloride  of  sodium.  Of  all  albuminous  substances, 
sulphate  of  magnesia,  precipitates  globuline  alone. 

To  determine  for  clinical  purposes  the  presence  of  globuline 
in  the  urine,  a  saturated  solution  of  sulphate  of  magnesia  is 
employed.    To  the  urine  previously  filtered  an  equal  quantity 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  149 

of  the  solution  is  added.  The  combined  fluids  are  to  be  well 
shaken  and  allowed  to  rest  for  twenty-four  hours,  when,  if 
globuline  is  present,  it  appears  as  a  floating  coagulum.  In  rare 
cases  it  subsides.  When  the  urine  is  distinctly  acid,  the  sulphate 
of  magnesia  solution  may  be  added  at  once.  When,  on  the 
other  hand,  it  is  but  feebly  acid  or  alkaline,  five  or  six  drops  of 
acetic  acid  should  be  added  for  100  c.c.  The  precipitate  thus 
obtained  is  easily  dissolved  by  common  salt. 

M.  Pohl*  gives  preference  to  sulphate  of  ammonia  over 
sulphate  of  magnesia.  In  testing  serous  liquids  he  adds  it 
directly,  and  to  acid  urines  after  neutralization  with  ammonia, 
and  separation  of  the  phosphates  by  filtration.  To  urine  thus 
rendered  alkaline  the  solution  of  sulphate  of  ammonia  is  to  be 
added.  After  an  hour's  repose,  the  precipitate  is  collected  on  a 
filter,  washed  with  sulphate  of  ammonia,  dried  at  100°  C,  and 
weighed.  The  whole  is  incinerated,  and  the  weight  of  the  ash 
subtracted. 

Quantitative  Analysis.  —  In  estimating  the  quantity  of 
globuline  in  any  given  specimen  of  urine,  the  albumen  must  be 
previously  removed,  and  vice-versa.  To  determine  primarily 
if  urine  contain  globuline,  a  certain  quantity  of  filtered  urine 
should  be  diluted  with  fifteen  or  twenty  times  its  bulk  of  water, 
and  a  few  drops  of  acetic  acid  added,  when,  if  globuline  is 
present,  a  turbidity,  or  even  a  precipitate,  results. 

Process  of  Hammar stein.— Filter  50  c.c.  (or  100  if  it  contain 
no  albumen).  The  reaction  ought  to  be  acid.  Mix  with  an 
equal  quantity  of  a  saturated  solution  of  sulphate  of  magnesia, 
and  lay  aside  for  twenty-four  hours,  when  flakes  of  globuline 
will  have  separated.  The  precipitate  is  carefully  collected,  the 
filter  paper  washed,  first  with  a  saturated  solution  of  sulphate 
of  magnesia,  and  then  with  boiling  alcohol  acidulated  with  acetic 
acid,  and  finally  with  boiling  distilled  water,  which  does  not 
dissolve  the  globuline  by  reason  of  the  addition  of  the  alcohol 
and  the  acetic  acid.  Dry  and  weigh.  The  globuline  may  be 
preferentially  estimated  by  difference.  Thus — the  albumen  and 
globuline  may  be  estimated  en  masse  by  coagulation.    Then  the 

*  Archiv.  fur  Kxper.  Pathol,  und  Rundschau  fur  die  Pharmacia, 
xiii.,  p.  369,  1887. 


150 


THE  URINE  IN  HEALTH  AND  DISEASE. 


globuline  may  be  separated  by  sulphate  of  magnesia,  and  the 
fluid  containing  only  albumen  filtered.  A  few  drops  of  acetic 
acid  are  then  added  and  the  albumen  coagulated.  From  the 
combined  weight  of  the  albumen  and  globuline  that  of  the 
albumen  alone  is  subtracted,  and  the  result  is  the  weight  of  the 
globuline.  The  amount  of  dilution  by  the  sulphate  of  magnesia 
solution  must  be  taken  into  account. 

Pathological  Significance. — Globuline  is  almost  invariably 
accompanied  by  albumen  in  the  urine,  and  is  usually  much  less 
abundant.  In  acute  nephritis  it  becomes  augmented*  coin- 
cidently  with  the  diminution  of  albumen,  and  considerable 
globinuria  is  of  grave  import,  and  a  diminution  of  its  elimina- 
tion of  favourable  augury. 

Fibrine. — When  the  urine  contains  blood,  it  necessarily 
contains  fibrine.  It  may  exist  independently  after  acute  in- 
flammatory affections  of  the  genito-urinary  tract  and  kidneys, 
and  appears  under  the  form  of  a  gelatinous  coagulum,  or  a  flaky 
mass  either  at  the  moment  of  emission  of  the  urine  or  shortly 
afterwards.  It  sometimes  exists  in  such  abundance  as  to  form 
with  the  urine  a  gelatinous  mass,  so  that  the  vessel  containing  it 
can  with  difficulty  be  emptied.  This  form  of  coagulable  urine 
is  more  frequently  met  with  in  warm  climates,  where  chyluria 
is  associated  with  fibrinuria.  Hoffmann  and  Ultzmann  have 
noticed  a  transitory  fibrinuria  in  certain  cases  of  villous  tumours 
of  the  bladder,  the  urine  being  of  a  reddish  or  pale  yellow 
colour.  In  cases  of  poisoning  by  cantharides,  especially,  fibrine 
is  apt  to  exist  in  the  urine. 

In  order  to  isolate  this  fibrine,  the  urine  is  filtered  and  the 
deposit  remaining  on  the  filter  washed  with  water.  This  is  in- 
soluble in  alkalies  and  diluted  acids. 

Mucine. — Murine  exists  in  the  secretions  of  all  the  mucous 
surfaces  of  the  body.  Normally,  it  exists  to  a  small  extent  in 
the  urine— 0*5  to  1*0  gramme  per  litre  according  to  Meisner. 
Its  proportion  is  increased  when  the  mucous  membrane  of  the 
urinary  tract  is  irritated,  as  in  catarrhal  affections  and  febrile 
affections  in  general.  The  mucus  normally  found  in  the  urine 
is  probably  secreted  by  itself  by  the  glands  at  the  Level  of  the 
*  Estelle,  Faveretj  and  Hoffmann. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  151 

trigonum  vesicce  ;  when  the  secretion  is  abnormally  abundant, 
it  is  probably  derived  from  the  ureters  and  secretory  structure  of 
the  kidney.  Mucus  existing  to  an  abnormal  extent  in  the  urine 
of  females  is  often  derived  from  the  vagina. 

Mucus  does  not  exist  in  the  urine  in  a  soluble  form,  and  may 
therefore  be  separated  from  it  by  nitration. 

Properties  of  Mucus. — Mucus  is  an  albuminous  substance  of 
a  white,  flaky  appearance.  It  absorbs,  and  becomes  swollen  by 
the  absorption  of,  water.  Dried  by  heat,  it  forms  a  gelatinous 
mass,  on  which  water  has  little  effect.  It  is  in  reality  insoluble 
in  water,  in  which,  however,  when  the  quantity  is  larger,  it  is 
capable  of  being  so  diffused  as  to  pass  through  a  filter  as  if  a 
solution.  Mucine  is  precipitated  by  acetic  acid,  and  the  precipi- 
tate is  unaffected  by  excess  of  the  acid.  Mucine  is  likewise 
precipitated  by  alcohol,  in  which  it  is  insoluble.  It  is  insoluble 
in  ether,  in  organic  acids,  and  in  dilute  mineral  acids,  while  it  is 
dissolved  by  the  concentrated.  Alkalies  readily  dissolve  mucine, 
notably  acetate  of  potash.  Sulphate  of  magnesia,  bichloride  of 
mercury,  neutral  acetate  and  sub-acetate  of  lead  also  precipitate 
it.  It  is  not  coagulated  by  heat,  and  on  heating,  acid  nitrate 
of  mercury  gives  with  it  a  bright  rose  colour. 

Analysis.  —  Microscopic  examination  does  not  reveal  the 
presence  of  mucus,  as  it  is  so  transparent  as  not  to  modify 
transmitted  light.  If  acetic  acid  be  previously  added,  micro- 
scopic examination  reveals  mucus  as  a  delicate  membrane  which 
is  coloured  by  tincture  of  iodine.  Sometimes  mucus  appears  in 
the  form  of  filaments,  which  may  be  mistaken  for  tube-casts, 
and  may  appear  opaque  from  a  deposit  on  them  of  urate  of  soda. 
They  are  distinguished  from  casts  by  their  size,  their  secondary 
ramifications,  and  their  association  with  epithelial  scales  and 
mucous  corpuscles.  Acetic  acid  renders  these  filaments  more 
apparent.  Urine  containing  an  excess  of  urates  is  precipitated 
by  acetic  acid,  the  precipitate  being  insoluble  in  an  excess  of 
acid,  but  on  being  heated  the  precipitate  disappears.  This  dis- 
tinguishes the  precipitate  from  mucus. 

When  the  urine  is  also  albuminous,  a  few  drops  of  acetic  acid 
should  be  added,  and  then  three  or  four  times  its  volume  of  con- 
centrated alcohol.    After  standing  for  some  time  the  fluid  is 


152 


THE  URINE  IN  HEALTH  AND  DISEASE. 


filtered  to  separate  the  albumen  precipitated  b}^  the  alcohol,  and 
the  nitrate  is  mixed  with  an  excess  of  acetic  acid. 

Leucomaines  and  Ptomaines.— According  to  Pouchet  and 
Gautier,  the  urine  always  contains  in  the  state  of  health  a  small 
proportion  of  leucomaines,  or  physiological  alkaloids.  These 
are  considerably  increased  in  infectious  diseases,  such  as  typhus 
fever,  and  certain  nervous  affections. 

Eobin  states  that  in  typhus  fever  the  urine  also  contains 
ptomaines,  or  cadaveric  alkaloids,  originating  in  perversion  of 
disintegration  or  bacterian  fermentation. 

PEPTONES. 

Peptones  are  the  result  of  the  complete  action  of  the  gastric 
juice  on  albuminous  substances.  By  hem/i-albumose  oy  propeptone 
is  understood  one  of  the  products  of  this  transformation.  These 
compounds  may  be  artificially  produced  by  means  of  pepsine  and 
pancreatine,  and  both  are  found  in  the  urine  under  certain  con- 
ditions, either  separately  or  in  combination  with  albumen. 

Properties  of  Peptones.— Peptones  are  white,  amorphous, 
and  slightly  bitter.  They  dissolve  with  facility  in  water,  are 
crvstallizable,  and  sparingly  soluble  in  alcohol.  They  are  in- 
soluble in  ether  and  chloroform.  They  are  not  precipitated  by 
heat,  like  albumen  and  globuline,  nor  by  ferrocyanide  of  potas- 
sium and  acetic  acid,  like  globuline,  albumen  and  hemi- 
albumose  ;  they  are  precipitated  by  tannin,  a  weak  solution  of 
hydrochloric  acid,  phosphotungstic  acid,  phosphomolybdic  acid, 
metaphosphoric  acid,  picric  acid,  bichloride  of  mercury,  nitrate 
of  mercury,  iodide  of  mercury  and  potassium  (Tanret's  solution)) 
nitrate  of  silver,  and  acetate  of  lead  in  ammoniacaJ  solution. 
On  heating  with  nitric  acid,  like  albumen,  they  give  the  coloured 
xanthoproteic  reaction,  and  with  caustic  soda  and  sulphate  of 
copper  solution  the  characteristic  red  biuret  reaction.  "With 
Millon's  solution  a  red  colour  is  produced,  as  in  the  case  of 
albumen,  but  of  much  greater  intensity. 

Analysis. — The  biuret  reaction  affords  the  best  evidence  of 
the  presence;  of  peptones  in  the  urine.  Should  the  urine  contain 
albumen,  it  should  be  acidulated  with  acetic  acid,  and  boiled 


ABNORMAL  CONSTITUENTS  OF  THE  UBINE.  153 


with  a  saturated  solution  of  chloride  of  sodium.  The  albumen 
is  separated  by  nitration  and  the  biuret  test  applied  to  the 
nitrate. 

Process  of  Hofmeister. — To  the  urine  2  percent,  of  acetate  of 
soda  is  added  and  perchloride  of  iron  guttatim  until  the  red  colour 
is  permanent.  Neutralize  the  urine  by  an  alkaline  solution,  and 
boil  until  all  the  iron  is  precipitated  in  the  form  of  a  basic 
acetate,  carrying  with  it  the  albumen.  The  filtrate  should  be 
entirely  free  from  albumen,  and  unaffected  by  the  ferrocyanide 
of  potassium  test.   The  special  peptone  tests  can  then  be  applied. 

Otherwise,  filter  about  half  a  litre  of  urine,  after  agitation 
with  a  little  neutral  acetate  of  lead  in  order  to  eliminate  and 
decolorize  mucine  if  present.  To  a  portion  of  the  filtered  fluid 
add  from  5  to  10  per  cent,  of  concentrated  hydrochloric  acid  and 
phosphotungstate  of  soda,  thus  : 

Phosphotungstate  of  soda         ...       ...    25  grammes. 

Hydrochloric  acid    5  ,, 

Distilled  water...    250  ,, 

Add  so  long  as  a  precipitate  is  formed  ;  filter  and  wash  the  pre- 
cipitate with  water  containing  4  or  5  per  cent,  of  concentrated 
sulphuric  acid  until  the  filtrate  is  colourless.  Add  an  excess  of 
solid  hydrate  of  baryta,  heat  gently  with  a  little  water  until  the 
fluid,  at  first  of  a  greenish  colour,  becomes  yellow,  filter  and  apply 
the  biuret  test.* 

Reaction  with  Tanret's  Solution. — Tanret's  solution  gives 
a  precipitate  with  peptones  which  disappears  on  the  application 
of  heat  and  reappears  on  cooling.  If  the  hot  test-tube  be  im- 
mersed in  cold  water  the  precipitate  appears  at  the  cooled  part. 

Reaction  with  Millon's  Solution. — Millon's  solution  gives  a 
cherry -red  colour  with  peptones. 

Reaction  with  Tannin,  etc. — Tannin,  bichloride  of  mercury 
and  chlorinated  water  give  an  abundant  white  precipitate  with 
peptones. 

Picric  Acid  Reaction. — Picric  acid  solution  gives  a  precipi- 
tate with  peptones  which  disappears  on  heating,  Albumen  may 
be  thus  separated  from  peptones  by  filtering  the  boiled  fluid  ;  the 

*  So  called  because  the  bicyanate  of  ammonia  gives  the  same 
coloration  when  applied  to  the  same  principles. 


154  THE  URINE  IN  HEALTH  AND  DISEASE. 


peptones  pass  through,  and  leave  the  coagulated  albumen  on  the 
filter.  If  the  urine  contain  alkaloids,  such  as  quinine,  picric 
acid  gives  a  similar  precipitate,  which  dissolves  on  heating.  If 
the  urine  contain  mucine,  as  shown  by  its  becoming  cloudy  on 
the  addition  of  acetic  acid,  it  should  be  separated  by  neutral 
acetate  of  lead. 

Pathological  Significance.— Peptones  are  found  in  the  urine 
in  cases  of  fibrinous  pneumonia,  acute  rheumatism,  phthisis, 
tubercular  meningitis,  puerperal  scepticaemia,  and  deep-seated 
abscesses  of  bone,  and  elsewhere,  especially  when  a  process  of 
absorption  has  been  established  (pyogenic  peptonuria  of  Von 
Jaksch) ;  in  pernicious  anaemia,*  progressive  paralysis,  and  scor- 
butus (haematogenetic  peptonuria  of  Von  Jaksch) ;  in  carcinoma 
of  the  stomach  and  in  typhoid  fever  (enterogenetic  peptonuria  of 
Maixner).  Peptonuria  is  evidently  caused  by  a  destruction  of 
leucocytes,  or  the  regression  of  plastic  exudation. 

Hemi-albumose  (Propeptone). — Hemi-albumose,  as  its  name 
implies,  is  a  compound  intermediate  between  albumen  and 
peptone.  It  was  first  described  by  Bence-Jones  as  occurring 
in  the  urine  in  the  case  of  osteo  -  malacia.  Subsequently 
Kiihne  and  Salkowsky  confirmed  this  observation.  Leube 
found  it  in  the  urine  in  a  case  of  urticaria,  Neale  in  a  case  of 
haemoglobinuria,  and  Von  Jaksch  in  a  case  of  tuberculosis  with 
nephritis  and  peritonitis. 

Properties. — Hemi-albumose  gives  most  of  the  albumen  re- 
actions, but  it  dissolves  with  difficulty  in  cold  solutions,  though 
rapidly  on  boiling,  by  which  it  is  contradistinguished  from 
albumen. 

Analysis. — If  an  excess  of  acetic  acid  be  added  to  urine  con- 
taining hemi-albumose  (and  neither  albumen  nor  globuline),  and 
fjuttatim  a  solution  of  ferrocyanide  of  potassium,  a  precipitate 
results,  which  disappears  on  heating.  Urine  rich  in  salts  ought 
to  be  previously  diluted.  By  saturating  such  urine  with  sea- 
salt,  a  precipitate  of  hemi-albumose  is  caused,  which  is  increased 
by  the  addition  of  acetic  acid,  and  entirely  disappears  on  heating, 
reappearing  on  cooling. 

Should  the  urine  simultaneously  contain  hemi-albumose, 
*  Neurol  Ctntralblatt  (No.  5,  1894). 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  155 

albumen,  and  globuline,  the  presence  of  hemi-albumose  is 
determined  as  follows  :  Saturate  the  urine  completely  with  a 
solution  of  marine-salt,  add  an  excess  of  acetic  acid,  boil  and 
filter.  The  albumen  and  globuline  remain  on  the  filter,  and  the 
hemi-albumose  passes  through,  and  separates  on  cooling.  The 
acetic  acid  and  ferrocyanide  of  potassium  test  may  also  be 
applied  to  the  filtrate. 

Transitory  Albuminuria.— The  subject  of  transitory,  or 
cyclical,  albuminuria  has  of  recent  years  received  considerable 
professional  attention,  and  various  conflicting  deductions  have 
been  drawn  from  the  occurrence.  The  merit  of  having  first 
directed  attention  to  albuminuria  independently  of  structural 
renal  change  is  usually  ascribed  to  Gubler,  in  1865  ;  but  as  long 
ago  as  1852  Dr.  Warburton  Begbie,  of  Edinburgh,  in  a  paper 
read  before  the  Medico- Chirurgical  Society  of  that  city,  drew 
attention  to  the  subject,  defining  temporary  albuminuria  as 
1  the  manifestation  and  continuance  of  albumen  in  the  urine 
during  a  limited  period,  and  unconnected  with  any  serious 
organic  change  in  the  kidney.'  The  literature  of  the  subject 
has  been  largely  added  to  since  then  by  many  well-known 
observers. 

The  percentage  in  which  albuminuria  occurs  in  obviously 
healthy  persons  has  been  variously  stated  by  authorities,  one 
author  (De  La  Celle)  estimating  it  as  high  as  84  per  cent. ;  but 
in  this  case  Tanret's  test  seems  to  have  been  relied  upon  for  the 
detection  of  albumen,  and  its  fallaciousness  as  an  albumen  test 
has  already  been  referred  to.  Dr.  Grainger  Stewart  (Brit.  Med. 
Jour.,  1887)  believes  that  albuminuria  exists  in  30  per  cent,  of 
the  community. 

In  seeking  for  an  explanation  of  albuminuria,  the  normal 
function  of  the  kidney  has  to  be  kept  in  view.  The  function  of 
the  Malpighian  body  is  that  of  filtration ;  that  of  the  cells  of 
the  convoluted  tubes  excretion — the  separation  of  the  urinary 
constituents  from  the  blood.  Accordingly,  Bernard  observed 
that  the  veins  in  the  glomeruli  contained  less  dark  blood  than 
the  veins  in  general,  the  arterial  blood  not  having  yet  parted 
with  its  vital  constituents.  Filtration  being  the  function  of  the 
glomeruli,  it  is  obvious  that  this  function  will  be  influenced  by 


156  THE  URINE  IN  HEALTH  AND  DISEASE. 


the  principles  and  conditions  affecting  osmosis  ;  hence  an  excess 
of  water  in  the  blood,  and  the  presence  of  alkalies,  will  stimulate 
the  act  of  nitration.  According  to  Heidenhain,  it  is  the 
external  layer  of  the  epithelium  of  the  Malpighian  capsule  that 
offers  resistance  to  the  passage  of  albumen.  If  this  layer  be 
supplied  with  impure  blood,  or  affected  by  certain  poisonous 
substances  introduced  into  the  blood,  it  undergoes  a  change 
(fatty  degeneration,  for  instance),  and  permits  of  the  transuda- 
tion of  albumen. 

The  vaso-motor  nerves  keep  the  bloodvessels  in  a  state  of 
moderate  contraction.  If  their  ganglia  are  stimulated  or 
irritated,  their  inhibitory  power  is  impaired,  and  dilatation  of  the 
vessels  ensues.  Under  these  circumstances  albuminuria  (vide 
1  Anatomy  and  Physiology  of  the  Kidney ')  is  apt  to  occur.  If 
the  cutaneous  capillaries  are  contracted,  increased  pressure  takes 
place  in  the  Malpighian  bodies,  and  diuresis  and  albuminuria 
may  result. 

Albuminuria,  in  the  sense  that  albumen  in  the  urine  is  not 
compatible  with  perfect  health,  must  always  be  considered  as  of 
pathological  significance,  though  not  necessarily  indicating 
structural  renal  change.  From  these  and  the  foregoing  observa- 
tions and  facts  the  following  conclusions  may  be  drawn  : 

(1)  That  the  presence  of  albumen  in  the  urine  of  apparently 
healthy  persons  is  of  frequent  occurrence. 

(2)  That  position  exercises  an  influence  on  the  secretion  of 
albumen,  the  horizontal  position  causing  its  diminution  or  total 
disappearance  in  the  urine,  it  being  apt  to  occur  on  rising,  and 
especially  after  breakfast — a  fact  capable  of  three  different 
explanations ;  (a)  The  sudden  dilatation  of  asthenic  bloodvessels 
and  interrupted  circulation  ;  (b)  the  effects  of  digestion  and 
gastro- intestinal  irritation,  and  possibly  an  undue  supply  of 
albumen  ;  and  (c)  that  the  alkaline  tide  is  highest  during  the 
morning  hours  (effect  on  osmosis). 

(3)  That  certain  diseases  (vide  p.  146)  so  alter  the  com- 
position of  the  blood  and  its  contained  albumen  that  the  vital 
relationship  between  it  and  the  Malpighian  capsule  is  changed, 
and  albumen  consequently  transudes  (dyscrasic  albuminuria). 
In  this  case  the  albumen,  according  to  Bouchard,  forms  a 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  157 


uniformly  cloudy  mass,  and  is  said  to  be  non-retractile,  in 
contradistinction  to  the  flaky  form  of  albumen  (retractile),  due 
to  renal  lesion,  and  coming  directly  from  the  blood.  As  a  rule, 
the  albumen  in  the  urine  arising  from  structural  renal  change  is 
not  precipitated  by  organic  acids  ;  in  cyclical  albuminuria,  on 
the  other  hand,  the  proteid  matter  is,  as  a  rule,  precipitated  by 
organic  acids. 

(4)  Bodily  exertion  notably  augments  the  proportion  of 
albumen  in  cases  of  transitory  albuminuria. 

(5)  Cold  bathing  causes  an  increase  of  the  albumen  in  the 
urine  in  transitory  albuminuria  by  increasing  the  vascular  renal 
pressure. 

(6)  Nervous  hyperexcitation  of  various  kinds  causes  temporary 
albuminuria,  such  as  protracted  intellectual  work  (often  in 
students),  excessive  irritation  and  exhaustion  of  the  genital 
centres  in  the  lumbar  region,  acting  reflexly  on  the  splanchnics, 
as  from  masturbation,  excessive  sexual  indulgence,  and  men- 
struation and  its  disorders.  Simple,  mental  emotion  may 
produce  a  similar  result,  as  in  the  case  mentioned  by  Basham 
of  a  man  subject  to  attacks  of  hematuria,  Mayer's  case  of  hema- 
turia as  a  sequel  to  a  fit  of  passion,  and  the  cases  cited  by 
Flirbringer  of  emotional  albuminuria. 

(7)  Transitory  albuminuria  is  more  frequent  among  children 
than  in  adults. 

(8)  Albuminous  urine  is  usually  above  the  specific  gravity 
of  1014. 

The  quantity  of  albumen  ehminated  in  various  diseases  ranges 
from  1  gramme  to  20  or  30  in  twenty-four  hours.  The  albumen 
is  said  to  be  in  small  amount  when  it  does  not  exceed  2 
grammes,  moderate  from  6  to  8,  and  considerable  when 
exceeding  from  10  to  12  grammes. 

Pathological  Significance. — As  to  prognosis,  the  absence  of 
tube-casts  and  a  high  specific  gravity  justify  a  favourable  prog- 
nosis. It  is  the  retention  of  urinary  products,  and  not  the  loss  of 
albumen  to  the  blood,  that  causes  death  in  albuminuria.  Cases 
have  been  known  in  which  albuminuria  existed  for  over  thirty 
years.  In  all  such  cases  the  specific  gravity  of  the  urine 
continues  high. 


158  THE  UKINE  IN  HEALTH  AND  DISEASE. 


GLUCOSE  (DIABETIC  SUGAR). 

History — Chemistry  of  Sugars — Tests  for  Sugar  in  the  Urine — Trom- 
mer's  Reaction — Fallacies  of  Trommer's  Test — Fehling's  Reaction — 
Fallacies  of  Fehling's  Test — Purdy's  Method  of  Estimating  Sugar  in 
the  Urine — Schmiedeberg's  Solution — Crismer's  Test — Bismuth  Re- 
action of  Bbttiger — Hoppe-Seyler's  Reaction — Almen's  Reaction — 
Indigo  Reaction — Phenyl-Hydrazine  Reaction — Agnosti's  Reaction 
— Picric  Acid  Reaction — Fermentation  Test — Specific  Gravity  of 
Diabetic  Urine — Quantitative  Analysis — Urine  containing  less 
than  5  per  cent.  Sugar. — Duhomme's  Quantitative  Analysis — Ap- 
proximate Estimate  of  Sugar  by  Specific  Gravity — Gerrard's  Per- 
centage Glycosometer  —  Optical  Quantitative  Analysis — Pathological 
Significance  —  Idiopathic  Glycosuria  —  Therapeutic  Indications  — 
Simulated  Glycosuria. 

C6H1206. 

Carbon    ...  ...  ...  ...  40'00 

Hydrogen  ...  ...  ...  6*66 

Oxygen   ...  ...  ...  ...  58*34 

100*00 

According  to  the  writings  of  Celsus,  Aretaeus  and  Galen,  the 
disease  termed  \  diabetes  '  (cia,  '  through,'  j3alvo,  1 1  go  ')  seems 
to  have  been  recognised  in  a  general  way  by  the  ancients.  The 
progressive  emaciation  characteristic  of  the  malady  was  observed 
as  being  accompanied  by  inordinate  thirst,  voracious  appetite, 
and  excessive  discharge  of  urine.  It  was  not,  however,  until  1674 
that  the  urine  in  certain  cases  was  discovered  to  possess  a  sweet 
taste,  and  the  honour  of  this  discovery,  on  which  followed  the  es- 
tablishing of  the  distinction  between  diabetes  insipidus  and  glyco- 
suric  diabetes,  is  due  to  Willis,  an  English  physician.  A  hundred 
years  subsequently,  Dobson,  of  Liverpool,  discovered  that  the 
blood  as  well  as  the  urine  contained  sugar  ;  and  he  inferred 
therefrom  that  this  sugar  was  separated  from  the  blood,  and  not 
formed  by  the  kidney.  In  1778  Cowley  separated  the  sugar 
from  the  urine  in  a  free  state.  In  1815  Chevreul  pointed  out 
that  the  sugar  existing  in  the  urine  in  cases  of  diabetes  mellitus 
was  different  from  cane  sugar  and  closely  resembled  that  of  the 
grape  ;  and  in  1825  Tiedmann  and  Gmelin  ascertained  that 
during  its  passage  along  the  alimentary  canal  starchy  matter 
was  transformed  into  sugar. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  159 


Normally,  sugar  is  found  in  the  small  intestine,  and  in  the 
chyle  after  the  ingestion  of  saccharine  or  starchy  matter,  and  in 
the  blood.  The  hepatic  vein  (Claude  Bernard)  abounds  in  it, 
while  it  does  not  exist  in  the  portal,  a  fact  demonstrating  the  sugar- 
forming  function  of  the  liver.  This  sugar  is  formed  from  an 
intermediate  albuminoid  product  called  glycogen,  belonging  to 
the  amyloid  group.  This  is  a  white  substance  which  iodine 
colours  violet-blue,  and  nitric  acid  transforms  into  xyloidine,  an 
explosive  material  like  gun-cotton.  Sugar  is  not  burned  off  in 
the  liver,  but  disappears  in  the  capillary  system,  after  under- 
going a  series  of  changes,  ultimately  represented  by  water  and 
carbonic  acid.  Temporary  glycosuria  may  be  occasioned,  accord- 
ing to  Frerichs,  by  (a)  poisoning  by  carbonic  oxide,  curara, 
nitrate  of  amyl,  and  large  doses  of  morphia,  chloral,  prussic 
acid,  sulphuric  acid  and  alcohol ;  (b)  by  digestive  derangements, 
catarrh  of  the  stomach,  cirrhosis  of  the  liver,  thrombosis  of  the 
portal  vein ;  (c)  by  derangements  of  the  nervous  system, 
neuralgia,  sciatica,  lesions  of  the  spinal  cord,  cerebral  excite- 
ment, disseminated  sclerosis,  apoplexy,  etc.  According  to  Worrh- 
Muller  cane-sugar,  grape-sugar  and  milk-sugar,  taken  in  doses 
of  from  50  to  250  grammes,  pass  directly  into  the  urine,  causing 
temporary  glycosuria.  Levulose,  taken  even  in  large  doses,  is 
never  found  as  such  in  the  urine. 

Milk-sugar  sometimes  appears  in  the  urine  after  child-birth, 
and  especially  when  the  secretion  of  milk  by  the  mammae  is 
embarrassed.  Hofmeister  and  Kaltenbach  have  also  found  it  in 
the  urine  of  infants  exclusively  fed  upon  milk. 

Bernard  has  caused  the  appearance  of  sugar  in  the  urine  by 
pricking  the  floor  of  the  fourth  ventricle.  It  is  sometimes 
alleged  that  sugar  exists  normally  in  urine  in  very  small 
quantity,  but  this  has  not  been  satisfactorily  demonstrated. 

Chemistry. — Sugars  are  divided  into  the  following  groups  : 


(Glucoses)  C6H1206 
(Saccharoses)  C^H^On 


(  Glucose,  or  Dextrose,  or  Grape -Sugar. 
(  Levulose. 

{ Cane-Sugar  or  Sucrose,  Maltose. 
Lactose  or  Milk-Sugar. 


(Amyloses  orAmyloids) 
C6H10O5 


160  THE  URINE  IN  HEALTH  AND  DISEASE. 


Fig.  34. — Tabular  Crystals  of 
Grape-Sugar. 


Glucose  (sugar  of  diabetes),  in  its  perfectly  pure  state,  is  of 
white  appearance.  It  most  frequently  presents  a  yellowish 
colour.  Its  crystalline  character  is  quite  different  from  that  of 
cane-sugar.  It  crystallizes  in  four  or  six  sided  rhomboidal 
prisms,  while  grape-sugar  occurs  in  small  cubes  or  square  plates. 

It  is  less  sweet  than  cane  sugar, 
and  less  soluble  in  water,  but 
more  soluble  in  alcohol.  It  is 
insoluble  in  ether.  Sucrose  and 
glucose  possess  right  -  handed 
rotation,  and  deviate  the  ray  of 
polarized  light  from  left  to  right 
according  to  the  amount  of  sugar 
present,   a   fact  by   which  its 

O amount  in  diabetic  urine  may  be 
estimated. 

Glucose  combines  readily  with 
caustic  alkalies,  forming  gluco- 
sates.  Thus  it  combines  with 
lime,  baryta  and  potash.  If  an  alcoholic  solution  of  potash  and 
glucose  be  mixed,  glucosate  of  potash  immediately  precipitates 
in  white  flakes.  If  the  mixture  be  subjected  to  heat,  it  becomes 
of  a  yellow  or  dark-brown  colour,  owing  to  the  formation  of 
glucic  and  melassic  acid,  according  to  the  quantity  of  glucose 
and  potash  present  (Moore-Heller's  Keaction). 

If  to  a  soluble  glucose  an  excess  of  potash  or  soda  be  added, 
and  a  solution  of  sulphate  of  copper,  the  result  is  a  bluish 
alkaline  liquor,  which,  on  being  heated,  gives  a  yellowish-red 
precipitate  of  protoxide  of  copper  (Cu20)  (reaction  of  Trommer, 
Fehling  and  Worm-Muller). 

Glucose  is  acted  on  by  mineral  acids,  by  which  it  is  trans- 
formed into  black  or  brownish  products.  Nitric  acid  oxidizes 
it,  forming  oxalic  (H2C204,  2H20)  and  saccharic  acid  (H2C6H808). 
Acted  upon  by  hydrochloric  or  sulphuric  acid,  cane-sugar  is 
converted  into  grape-sugar.  This  is  easily  demonstrated  in  the 
following  manner :  Dissolve  a  few  grains  of  cane-sugar  in  water 
in  a  test-tube.  Add  a  few  drops  of  a  solution  of  sulphate  of  copper 
and  a  considerable  quantity  of  a  solution  of  potash,  and  heat  the 


ABNOBMAL  CONSTITUENTS  OF  THE  URINE.  161 

mixture  to  the  boiling-point.  No  change  occurs.  To  another 
portion  of  the  sugar  solution  add  a  drop  of  sulphuric  acid,  and 
boil  for  ten  or  twenty  minutes.  Add  the  solution  of  sulphate  of 
copper  and  potash  as  above,  boil,  and  a  yellowish-red  precipitate 
of  cuprous  oxide  (CuaO)  immediately  falls.  Here  the  acid  has 
converted  the  cane-sugar  (CiaHMOu)  into  '  invert  sugar '  (a 
mixture  of  dextrose  and  levulose),  so-called  because  it  rotates  a 
ray  of  polarized  light  to  the  left,  whereas  cane-sugar  is  dextro- 
rotatory. 

C^H^On-f-HoO  ==  C0H12O6  -f  C6H1206 

Both  cane-sugar,  maltose  and  grape-sugar  yield  alcohol  and 
carbonic  acid  by  fermentation.  The  cane-sugar  probably  always 
passes  into  grape-sugar  before  the  production  of  alcohol  begins. 

C6H1206  =  2C2H5OH  +  2C02 
(Grape-sugar)    (Alcohol)    (Carbonic  Acid) 

Extraction  of  Glucose  from  Diabetic  Urine. — Evaporate 
the  urine  on  a  water-bath  until  it  is  of  a  syrupy  consistence  ; 
leave  it  to  settle  in  a  cold  place,  when,  at  the  expiry  of  a  few 
days,  a  crystalline  deposit  will  have  formed.  By  treating  these 
crystals  with  absolute  alcohol,  urea  and  extractive  matter  are 
separated.  They  are  then  dissolved  in  boiling  alcohol  and 
the  solution  evaporated. 

TESTS  FOR  SUGAR  IN  THE  URINE. 

Moore's  Reaction.  —  Equal  quantities  of  non  -  albuminous 
urine  and  a  solution  of  caustic  potash  are  to  be  mixed  in  a  test- 
tube.  The  earthy  phosphates  are  first  precipitated,  and  may  be 
separated  by  filtration.  The  fluid  is  then  boiled,  when,  if  it 
contain  sugar,  it  assumes  a  colour  passing  from  pale  yellow  to 
dark  brown.  The  colour  is  due  to  the  successive  formation  of 
glucic  and  melassic  acids,  and  disappears  on  the  addition  of  a 
few  drops  of  nitric  acid,  the  characteristic  odour  of  caramel  being 
evolved.  For  the  purpose  of  comparison,  it  is  better  to  confine 
the  action  of  heat  to  the  upper  portion  of  the  tube.  Unless  the 
urine  contain  a  considerable  quantity  of  sugar  (3  per  cent.,  or 
1^  grains  to  the  ounce),  the  test  is  not  sufficiently  discriminating. 

11 


162  THE  URINE  IN  HEALTH  AND  DISEASE. 


Bouchardat  prefers  lime  to  the  potash  solution,  as  the  latter 
colours  many  of  the  extractive  matters  of  the  urine. 

Fallacies  of  Moore's  Test.  —Urine  containing  the  pigments  of 
rhubarb  and  senna  becomes  reddish-brown  on  the  addition  of 
alkalies  when  cold.  Urine  containing  pyrocatechin  becomes 
brown  on  exposure  to  air,  especially  after  the  addition  of  an 
alkali. 

Trommer's  Eeaction. — This  test  is  based  on  the  property 
which  grape  -  sugar  possesses  of  reducing  oxide  of  copper  in 
alkaline  solutions  by  the  aid  of  heat.  To  about  5  c.c.  of  filtered 
urine  free  from  albumen  (it  is  not  necessary  to  remove  the 
albumen  if  it  does  not  exceed  0*2  per  cent.),  add  from  1  to  2  c.c. 
of  a  10  per  cent,  solution  of  potash  or  soda.  A  10  per  cent, 
solution  of  sulphate  of  copper  is  added  drop  by  drop  until  the 
bluish  precipitate  of  hydroxide  of  copper  ceases  to  dissolve.  If 
the  urine  contain  sugar,  a  considerable  quantity  of  the  oxide  of 
copper  is  dissolved,  and  the  liquor  assumes  an  azure  blue 
appearance.  Heat  is  applied  to  the  boiling-point,  when,  towards 
the  upper  portion  of  the  tube,  a  yellowish -red  precipitate  of 
protoxide  of  copper  appears.  The  heat  is  then  withdrawn,  and 
the  reaction  continues  to  extend  throughout  the  liquid.  This 
reaction  is  sufficiently  marked  when  the  proportion  of  sugar  is 
not  under  0*2  to  0*3  per  cent. 

Fallacies  of  Trommer's  Test. — Trommer's  test  is  not  reliable 
when  the  quantity  of  grape-sugar  is  small.  Uric  acid,  creatinine, 
and  certain  extractive  matters,  reduce  the  copper  solution  when 
the  sugar  is  absent,  and  especially  if  the  urine  be  concentrated. 
The  reduction  by  these  substances,  generally  speaking,  takes 
place  only  at  the  boiling-point.  Exception,  however,  is  to  be 
noted  in  the  case  of  uric  acid,  a  precipitate  of  oxide  of  copper 
often  forming  at  90°  or  100°  Fah.  In  consequence  of  this  source 
of  fallacy,  too  strong  heat  should  not  be  employed,  nor  should 
its  action  be  long  continued.  In  some  cases,  secondary  reduction 
of  the  copper  takes  place.  This  does  not  indicate  the  presence 
of  sugar,  as  the  action  in  this  case  is  immediate.  Trommer's 
test  has  thus  to  be  performed  with  care.  In  doubtful  cases, 
only  a  few  drops  of  the  solution  of  copper  (1  to  3)  should  be 
added.    If,  on  the  application  of  heat,  reduction  is  manifested 


ABNOKMAL  CONSTITUENTS  OF  THE  URINE. 


163 


by  decoloration,  more  solution  has  to  be  added,  until  a  decided 
reaction  is  produced. 

Fehling's  Reaction. — This  test  is  also  based  on  the  reduction 
of  an  alkaline  solution  of  copper  by  glucose.  The  solution  is 
prepared  as  follows :  34*65  grammes  of  pure  dry  crystals  of 
ordinary  sulphate  of  copper  are  dissolved  in  about  250  c.c.  of 
distilled  water ;  173  grammes  of  pure  crystals  of  double  tartrate 
of  potash  and  soda  (sel  de  Seignette)  are  dissolved  in  480  c.c. 
of  a  solution  of  caustic  soda  of  sp.  gr.  1*14.  The  solutions  are 
mixed,  and  water  added  to  1  litre.  A  clear,  deep  blue  solution  is 
thus  obtained,  Fehling's  solution,  of  which  100  c.c.  represent 
3*464  grammes  of  sulphate  of  copper,  and  correspond  to  0*5  of  a 
gramme  of  pure  anhydrous  grape-sugar,  0*475  of  cane-sugar, 
0*82  of  maltose,  and  0*45  of  starch. 

Place  5  or  6  c.c.  of  Fehling's  solution  in  a  test-tube,  and  boil. 
If  there  is  no  precipitate,  which  shows  that  the  reagent  is  pure, 
the  suspected  urine  is  added  by  pouring  it  carefully  along  the 
tube,  so  as  to  be  superimposed  on  the  test  solution.  If  sugar  be 
present,  on  boiling  a  greenish  layer  first  appears,  rapidly  passing, 
through  yellow,  to  orange  or  red,  the  precipitate  extending  to  the 
entire  fluid.  If  the  sugar  be  in  small  quantity,  the  fluid  must  be 
boiled  for  a  few  minutes.  This  method  is  preferable  to  adding 
tjie  reagent  to  the  boiling  urine. 

Modification  of  Fehling's  Solution,  by  Ost* — The  solution 
recommended  by  M.  Ost  contains  per  litre,  crystallized  sulphate 
of  copper  23*5  grammes,  dry  carbonate  of  potash  250  grammes, 
bicarbonate  of  potash  100  grammes.  This  solution  offers  the 
following  advantages  over  Fehling's  solution :  It  can  be  kept 
without  undergoing  change,  and  it  less  profoundly  decomposes 
the  sugars  during  determination.  50  c.c.  of  this  solution  corre- 
spond to  100  milligrammes  of  inverted  sugar,  102*5  milligrammes 
of  dextrose,  90  milligrammes  of  levulose,  and  117  milligrammes 
of  galactose. 

Fallacies  of  Fehling's  Test. — If  Fehling's  solution  be  too  long 
kept,  it  spontaneously  undergoes  a  process  of  reduction.  This 
is  said  to  be  due  to  the  formation  of  racemic  or  paratartaric  acid, 
into  which  exposure  converts  the  tartaric  acid.    If  no  precipitate 
*  Zeitschrift  fur  Anal.  Chemie,  xxxix.  (1891). 


164  THE  UEINE  IN  HEALTH  AND  DISEASE. 

occur  with  Fehling's  solution  on  boiling,  its  delicacy  is  unimpaired ; 
but  if  so,  a  little  more  potash  or  soda  should  be  added,  and  the 
liquid  filtered,  when  it  is  again  available.  It  is  sometimes 
recommended  to  keep  the  copper  and  the  alkaline  solutions 
separately,  and  mix  only  when  required  for  use ;  but  this  is 
quite  unnecessary  if  the  foregoing  precautions  be  observed. 

The  addition  of  glycerine  to  Fehling's  solution  has  been  recom- 
mended for  longer  preservation,  but  it  must  be  remembered  that 
the  glycerine  of  commerce  is  almost  invariably  impure. 

In  employing  Fehling's  solution,  any  albumen  contained  in 
the  urine  must  be  separated  by  coagulation  by  heat,  or  precipita- 
tion by  subacetate  of  lead.  If  the  urine  contain  albumen,  the 
reduction  is  prevented,  and  the  fluid  becomes  of  a  violet  colour. 
The  presence  of  ammoniacal  salts  also  interferes  with  the  reduction, 
a  part  of  the  soda  of  the  '  Fehling '  being  used  up  by  the  salts. 
Should  the  urine  have  undergone  ammoniacal  fermentation,  it 
should  be  boiled  with  a  solution  of  caustic  soda  so  long  as 
ammonia  is  given  off.  It  may  subsequently  be  tested  for  sugar. 
Uric  acid  and  urates  also  cause  a  reduction  of  the  copper, 
especially  after  protracted  boiling  and  during  the  process  of 
cooling.  This  source  of  error  may  be  evaded  by  treating  the 
urine  with  subacetate  of  lead,  which  removes  albumen  and 
urates.  Any  quantity  of  sugar  exceeding  3  id  4  per  1000  is 
readily  detected  by  Fehling's  solution  ordinarily  employed. 

It  sometimes  happens  that  glucose  in  diabetic  urine  is  replaced 
by  dextrine.  In  this  event,  according  to  Bouchardat,  the  copper 
reduction  takes  place  only  after  prolonged  boiling. 

The  urine  of  individuals  taking  turpentine,  copaiba,  chloroform, 
chloral,  camphor  and  cubebs,  reduces  the  copper  solution.  Pyro- 
catechin, benzoate  of  soda,  and  glycerine,  also  reduce  'Fehling.' 

The  precipitate  of  the  phosphates  caused  by  the  mixing  of  the 
two  fluids  sometimes  persists  in  a  state  of  fine  division,  and  may 
be  mistaken  for  copper  reduction.  The  colour  of  the  precipitate 
is,  however,  different,  and  after  a  few  minutes'  repose  the  phos- 
phates settle  in  the  bottom  of  the  tube,  while  the  copper  sub- 
oxide remains  suspended  for  many  hours. 

Purdy's  Method  of  Estimation  of  Sugar  in  the  Urine.— 
Instead  of  Fehling's  solution,  this  author  employs  the  following : 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  165 


Pure  sulphate  of  copper        ...       ...       ...         4*15  grm. 

Pure  mannite   ...       ...       ...       ...       ...  10 

Caustic  potash  ...       ...       ...       ...       ...       20*40  ,, 

Aramonia  (D  =  0*880)   30  „ 

Glycerine         ...       ...       ...       ...       ...       50  c.c. 

Distilled  water  q.s.  to  ...       ...       ...       ...  1000 

The  sulphate  of  copper  is  first  dissolved  in  water,  and  the 
glycerine  and  mannite  are  then  added ;  the  potash  is  separately 
dissolved  in  water,  and  after  cooling  the  two  solutions  are 
mixed.  The  ammonia  is  added,  the  solution  is  carefully  filtered, 
and  distilled  water  is  added  to  make  the  solution  up  to  a  litre. 
25  c.c.  of  this  solution  are  reduced  by  15  milligrammes  of  glucose  ; 
the  deep  blue  coloration  disappears,  and  the  result  is  a  perfectly 
clear,  colourless  liquid.  The  copper  solution  should  be  heated  in 
a  capsule  to  the  boiling-point,  and  the  urine  added  drop  by  drop 
at  intervals  of  from  two  to  three  seconds.  The  results  are  very 
accurate.  If  the  sugar  is  in  great  quantity,  the  urine  should  be 
diluted  with  water  {Pliarm.  Zeitsch.fur  Buss.,  xix.,  1890). 

Schmiedeberg's  Solution.*  —  In  Schmiedeberg's  formula, 
mannite  replaces  the  potassio-tartrate  of  soda.  The  solution  is 
prepared  as  follows  :  Dissolve  34*632  parts  of  crystallized  sulphate 
of  copper  in  200  c.c.  of  water,  and  15  grammes  of  pure  mannite 
in  100  c.c.  of  water.  These  two  solutions  are  combined,  and 
480  c.c.  of  a  solution  of  caustic  soda,  sp.  gr.  1*145,  added,  and 
sufficient  water  to  make  1000  c.c.  According  to  Schmiedeberg, 
this  solution  keeps  better  than  Fehling's. 

Crismer's  Test.— M.  Crismer  has  recently  advocated  the  use 
of  safranin  as  a  test  for  sugar.  If  1  c.c.  of  saccharine  urine  be 
heated  to  ebullition  with  5  c.c.  of  a  solution  of  safranin  and 
2  c.c.  of  caustic  potash  solution,  discoloration  of  the  safranin  at 
once  takes  place.  On  cooling,  the  solution  becomes  turbid. 
This  reaction  has  the  advantage  over  Fehling's  solution  in  not 
being  decolorized  by  uric  acid,  creatinine,  chloral,  chloroform, 
peroxide  of  hydrogen,  nor  the  hydroxylamine  salts.  Albumen 
decolorizes  it  but  slowly. 

Bismuth  Reaction  of  Bottiger. — If  a  solution  of  glucose 
with  a  concentrated  solution  of  caustic  soda  or  carbonate  and 

*  Journal  de  Pharmacie  de  1' Alsace- Lorraine,  January,  1886. 


166  THE  URINE  IN  HEALTH  AND  DISEASE. 


a  little  nitrate  of  bismuth  be  heated  together  to  the  boiling- 
point,  metallic  bismuth*  is  obtained  as  a  fine  black  powder. 
This  reaction  demonstrates  the  presence  of  0*1  per  cent,  of 
sugar.  Nitrate  of  bismuth  is  neither  reduced  by  uric  acid  nor 
creatinine,  but  it  is  reduced  on  prolonged  heating  by  other 
indeterminate  substances.  In  albuminous  urines  a  sulphide  of 
bismuth  may  be  produced  by  this  test.  Albumen  should, 
therefore,  be  previously  separated. 

Hoppe-Seyler's  Reaction,  f — The  following  reagent  is  recom- 
mended by  Hoppe-Seyler.  The  reaction  is  based  on  the  forma- 
tion of  O-nitrophenyl-  propionic  acid  from  indigo,  when  the 
latter  is  boiled  with  an  alkali  and  a  reducing  substance.  The 
process  is  as  follows  :  Take  5  c.c.  of  a  half  per  cent,  solution  of 
O-nitrophenyl-propionic  acid  in  soda  and  water,  and  boil  during 
thirty  seconds  with  ten  drops  of  the  urine  to  be  examined.  If 
the  mixture  becomes  of  a  deep  blue,  it  contains  a  reducing 
substance  equal  to  at  least  0*5  per  cent,  of  sugar.  Normal  urine 
thus  treated  becomes  of  a  green  colour.  The  presence  of 
albumen  in  urine  does  not  prevent  this  reaction,  and  the 
minutest  quantity  of  sugar  is  thus  detected. 

Almen's  Reaction. — This  reagent  is  made  according  to  the 
following  formula :  10  grammes  of  nitrate  of  bismuth,  40 
grammes  of  crystallized  nitrate  of  potash  and  soda,  62  grammes 
of  caustic  potash  and  distilled  water  to  500  c.c.  About  5  c.c.  of 
the  urine  are  mixed  with  from  0*5  to  1  c.c.  of  Almen's  liquor, 
and  heated  to  boiling  for  one  or  two  minutes.  If  the  urine 
contain  a  moderate  amount  of  sugar,  it  becomes  of  a  dark 
colour,  which  deepens  with  the  continuance  of  heat  until  it 
becomes  brownish  black.  This  test  demonstrates  the  existence 
of  from  0*1  to  0*05  per  cent,  of  sugar. J  After  the  ingestion  of 
turpentine  and  rhubarb,  it  gives  with  the  urine  a  similar  black 
colour,  in  the  latter  case  due  doubtless  to  its  action  on  chryso- 
phanic  acid. 

Indigo  Reaction. — In  order  to  apply  this  test,  any  albumen 
*  Probably  mixed  with  Bismuth  oxide. 

+  1  Ueber  eine  Reaktion  ziim  Nachweis  von  Zucker  im  Urin,  Auf 
Indigobildung,'  Zeitschrift  f.  Physiolocj.  Chemie,  1892,  t.  xvii.,  p.  83. 

t  Annal.  de  la  Society  Med.  Chir.  de  Litye,  et  Repertoire  de 
Pharmacie,  March,  1889. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  167 


which  the  urine  may  contain  must  be  removed  by  precipita- 
tion and  filtering.  It  must  then  be  rendered  alkaline  by  a 
solution  of  bicarbonate  of  soda.  A  solution  of  indigo  is  then 
added  to  the  extent  of  causing  a  well-marked  blue  colour.  On 
being  heated,  the  liquor,  if  it  contains  sugar,  becomes  almost 
completely  decolorized,  passing  through  violet,  purple-red,  red, 
yellow  to  pale  yellow,  and  on  exposure  to  the  air  it  resumes  its 
original  colour,  passing  inversely  through  the  foregoing  shades 
of  colour  (Mulder's  reaction). 

Phenyl-Hydrazine  Eeaction. — This  test  is  as  follows:  A 
small  portion  of  hydrochlorate  of  phenyl-hydrazine  with  twice 
the  quantity  of  sodium  acetate  is  placed  in  a  test-tube  half  filled 
with  water,  and  warmed.  After  adding  an  equal  volume  of  the 
solution  to  be  tested,  the  mixture  is  boiled  for  twenty  minutes, 
when,  on  cooling  (sugar  being  present),  yellow  crystalline  needles 
of  a  compound  of  glucose  and  phenyl-hydrazine  (phenyl-gluco- 
sazine)  are  deposited.  These  crystals  have  a  definite  melting- 
point  of  204°  to  205°  C.  This  is  a  very  delicate  test,  and  is 
applicable  to  the  detection  of  very  small  quantities  of  sugar.  In 
normal  urine,  in  the  hands  of  Von  Jaksch,  a  negative  result  was 
always  obtained  with  this  reagent. 

Agnosti's  Reaction. — To  detect  glucose  in  aqueous  solutions 
Agnosti  recommends  the  following :  Five  drops  of  chloride  of 
gold  (1  per  1,000)  and  two  drops  of  a  5  per  cent,  solution  of 
caustic  potash  are  added  to  the  suspected  fluid.  It  is  then  boiled, 
when,  on  cooling,  if  it  contain  glucose,  it  assumes  a  violet  colour 
if  the  solution  be  aqueous,  and  a  port-wine  colour  if  of  urine. 
The  other  elements  of  the  urine  do  not  give  this  reaction.  If 
albumen  be  present,  it  should  be  previously  removed. 

Picric  Acid  Reaction. — A  solution  of  potash  and  a  few  drops 
of  picric  acid  solution  added  to  saccharine  urine  cause  a  deep-red 
coloration,  due  to  the  formation  of  picraminic  acid. 

Fermentation  Test. — To  apply  this  test  two  flasks  are  taken 
(Fig.  35)  :  Into  the  flask  A  from  20  to  30  centimetres  of  urine  are 
introduced,  with  a  little  yeast  and  a  pinch  of  tartaric  acid.  The 
neck  of  the  flask  is  closed  with  a  cork  pierced  by  two  tubes,  the 
tube  a  passing  to  the  bottom  of  the  flask,  and  a  second  tube  (c) 
connecting  with  B,  and  passing  to  an  equal  depth.    The  flask  B 


168 


THE  URINE  IN  HEALTH  AND  DISEASE. 


is  half  filled  with  a  solution  of  lime  or  baryta,  and  the  orifice  (6) 
of  the  tube  a  is  sealed  with  a  piece  of  wax.  The  apparatus  is 
placed  in  an  atmosphere  with  a  temperature  of  15°  to  20°  C. 
(59°  to  77°  Fahr.).  Within  twelve  hours  fermentation  will  take 
place,  as  evinced  by  the  evolution  of  carbonic  acid  gas  from  the 
flask  A,  and  the  formation  of  a  precipitate  of  carbonate  of  lime 
or  baryta  in  the  flask  B.  To  be  certain  that  the  carbonic  acid 
does  not  proceed  from  the  decomposition  of  the  yeast  alone,  the 
experiment  should  be  repeated,  employing  pure  water  instead  of 
the  fluid  supposed  to  contain  sugar.  Theoretically,  48*89  parts 
of  carbonic  acid  correspond  to  100  of  glucose  ;  but  according  to 


Pasteur,  not  only  are  alcohol  and  carbonic  acid  formed  in  the 
process  of  alcoholic  fermentation,  but  likewise  a  little  glycerine 
and  succinic  acid.  Hence  in  practice  it  is  found  that  48*88  cor- 
respond to  100  parts  of  glucose.  Sir  William  Koberts  has  shown 
that  after  fermentation  '  the  number  of  degrees  of  "  density  lost " 
indicated  as  many  grains  of  sugar  per  fluid  ounce.' 

Specific  Gravity  of  Diabetic  Urine.— While  a  high  specific 
gravity  does  not  absolutely  demonstrate  the  presence  of  sugar  in 
urine,  when  it  exceeds  1036,  in  pale  urine,  the  chances  are 
largely  in  favour  of  the  presence  of  sugar. 


Fig.  35. — Fermentation  Apparatus. 


ABNOBMAL  CONSTITUENTS  OF  THE  URINE.  169 


Quantitative  Analysis. — The  amount  of  sugar  contained  in 
any  solution  may  be  determined  chemically  or  optically.  In  the 
former  method,  which  is  absolutely  accurate,  Fehling's  solution 
is  conveniently  employed  as  a  standard  reagent.  One  c.c.  of 
this  solution  is  reduced  by  0*005  of  glucose  (10  c.c.  are  con- 
sequently equal  to  0*05).  Into  a  porcelain  capsule  pour  10  c.c. 
of  Fehling's  solution,  which  dilute  with  40  c.c.  of  water.  Into 
a  burette,  graduated  to  tenths  of  a  c.c,  put,  for  example,  10  c.c, 
of  urine,  diluted  with,  say,  five  times  its  volume  of  water.  The 
Fehling's  solution  is  now  completely  boiled  over  a  spirit-lamp  ; 
and  the  diluted  urine  from  the  burette  carefully  mixed  with  it, 
until  the  decoloration  is  complete,  and  a  red  precipitate  of 
oxide  of  copper,  or  a  yellow  one  of  the  hydrated  oxide,  appears. 
On  referring  to  the  burette,  suppose  you  find,  for  example, 
that  9  c.c.  of  the  diluted  urine  have  been  used  to  effect  this 
change,  then  1*5  c.c.  of  pure  urine  reduces  10  c.c.  of  Fehling's 
solution ;  and  as  10  c.c.  of  Fehling  correspond  to  0'05  grammes 
of  glucose,  1*5  c.c.  of  this  urine  must  contain  0*05  grammes 
of  glucose,  =  33-33  gms.  per  litre  (1-5  :  1000  :  :  0'05  :  33*33).  In 
order  to  obtain  exact  results  in  this  experiment,  the  urine  must 
be  previously  filtered,  any  albumen  separated,  and  it  ought  to 
be  so  diluted  as  to  contain  not  more  than  5  per  cent,  of  sugar, 
It  is  important  to  note  when  the  blue  colour  has  completely  dis- 
appeared, and  complete  reduction  of  the  copper  has  taken  place. 
To  determine  this,  the  fluid  is  to  be  rapidly  filtered,  and  one 
portion  of  it  boiled  with  Fehling's  solution,  and  another  with 
diluted  urine.  No  precipitate  should  result  in  either  case.  If  in 
the  first  instance  a  precipitate  forms,  it  is  obvious  that  too  much 
urine  has  been  added,  and  in  the  second,  not  sufficient.  The 
experiment  should  be  repeated,  and  the  mean  of  successive 
trials  taken  in  order  to  obtain  conclusive  results.  Or  if  to  about 
1  c.c.  of  the  filtered  fluid  a  few  drops  of  a  solution  of  ferrocyanide 
of  potassium  be  added,  and  a  brown  colour  results,  it  is  shown 
that  non-reduced  copper  still  exists. 

Urine  containing  less  than  5  per  Cent,  of  Sugar.— While, 
on  the  one  hand,  if  the  urine  be  rich  in  glucose,  it  is  better  to 
dilute  the  solution  so  as  to  contain  about  10  grammes  per  litre, 
on  the  other,  if  the  proportion  is  below  5  per  cent.,  the  influence 


170  THE  URINE  IN  HEALTH  AND  DISEASE. 

of  other  substances,  which  interfere  with  the  copper  reduction,  is 
more  appreciable;  hence  it  is  necessary  to  purify  the  urine  by 
treating  it  with  basic  acetate  of  lead  in  the  following  manner  : 
To  10  c.c.  of  urine  in  a  graduated  burette,  add  a  tenth  of  its 
volume  of  subacetate  of  lead  ;  shake  well,  and  filter.  To  remove 
the  lead,  a  weak  solution  of  carbonate  of  soda  should  be  added 
to  make  the  volume  equal  to  50  c.c. ;  mix  well,  filter,  and  apply 
the  Fehling  test. 

• 

Table  indicating  the  Amount  of  Sugar  per  Litre  in  Urine 
estimated  by  Fehling's  Solution. 


Quantity  of 
Fehling's 

C.C.  of  Urine 

Amount 

Quantity  of 
Fehling's 

C.C.  of  Urine 

Amount  of 

necessary  to  of  Glucose  per 

necessary  to 

Glucose  per 

Solution. 

decolorize. 

Litre. 

Solution. 

decolorize. 

Litre. 

Gr. 

Gr. 

ro 

50 

12*5 

4'00 

1-5 

33-33 

13-0 

3-84 

2-0 

25 

]4-0 

3-75 

2-5 

20 

15  0 

3  33 

3-0 

16-66 

16-0 

3-12 

c 

3.5 

14-275 

C 

170 

2-94 

.2 
".3 

4-0 

1250 

.2 

18-0 

277 

4'5 

11-11 

19-0 

2  63 

"o 
m 

5-0 

10 

Ul 

20-0 

2-50 

w 

5-5 

9-09 

QQ 

21*0 

2-38 

& 

6-0 

8-33 

~b0 

.5 

22-0 

2  27 

6-5 

7*69 

23*0 

2-17 

PR 

CM 

7-0 

7-11 

24-0 

2-08 

7-5 

6-66 

25-0 

2-00 

o 

8-0 

6*25 

o 

30-0 

1665 

6 

8-5 

5-88 

6 

35-0 

1-428 

b 
o 

9-0 

5-55 

6 

40-0 

1-25 

i—i 

9-5 

5-25 

o 
i— ( 

45  0 

111 

10-0 

5 

50-0 

1-00 

30*5 

4-76 

60-0 

0-83 

11-0 

4-54 

70-0 

071 

11-5 

4-34 

80-0 

063 

12 

4-15 

90-0 
100-0 

055 
0--50 

Duhomme's  Quantitative  Analysis.— In  this  process  the 
chemical  principles  are  the  same  as  in  that  by  Fehling's  solution, 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  171 

but  the  apparatus  and  subsequent  calculations  are  different,  and 
both  are  exceedingly  simple.  This  method  is,  therefore,  admir- 
ably adapted  for  clinical  purposes.  The  apparatus  required 
consist  of  some  ordinary  test-tubes,  and  two  of  Limousin's 
pipettes  graduated  to  1  and  2  c.c.  respectively.  Like  all  other 
fluids  of  the  economy,  the  urine  varies  in  composition  and  specific 
gravity  from  time  to  time.  With  these  varying  conditions,  the 
number  of  drops  contained  in  a  given  amount  of  urine — say, 
1  c.c. — will  correspondingly  vary.  A  pipette  is  filled  to  the 
extent  of  2  c.c.  with  Fehling's  solution,  which  are  transferred  to 
a  test-tube,  and  diluted  with  an  equal  quantity  of  liquor  sodae, 
or  water,  which  does  equally  well.  A  centimetre  of  urine  is 
drawn  into  another  pipette,  and  the  number  of  drops  which  it 
contains  is  estimated,  in  the  first  instance,  by  allowing  the  fluid 
to  escape  guttatim  from  the  pipette,  by  exercising  gentle  pressure 
on  its  indiarubber  cap.  No  further  measurement  is  required 
for  that  urine,  as  with  the  same  pipette  the  number  of  drops  will 
always  be  the  same.  The  number  of  drops  in  1  c.c.  being  ascer- 
tained— say,  e.g.,  24  drops — the  urine  pipette  is  again  filled, 
and  the  2  c.c.  of  '  Fehling  '  are  boiled,  and  its  decoloration 
produced  drop  by  drop  by  the  saccharine  urine.  If  8  drops,  e.g., 
are  found  to  have  decolorized  the  2  c.c.  of  '  Fehling,'  then  this 
amounts  to  ^  of  a  c.c,  and  2  c.c.  of  'Fehling'  correspond  to 
1  centigramme  of  glucose.  Rule  :  Multiply  the  number  of  drops 
contained  in  1  c.c.  of  urine  by  10,  and  divide  the  product  by  the 
number  of  drops  required  to  decolorize  2  c.c.  of  '  Fehling,'  and 
the  quotient  will  represent  the  number  of  grammes  and  centi-. 
grammes  of  sugar  per  litre  (8  :  24  :  :  1  :  3,  and  3  x  1000= 
3000-^100=30  grammes;  i.e.,  if  1  c.c.  of  urine  contain  3  centi- 
grammes, a  litre  must  contain  30  grammes). 

Approximate  Estimate  of  Sugar  by  Specific  Gravity.— 
According  to  Bouchardat,  the  amount  of  sugar  in  urine  may  be 
approximately  determined  as  follows :  The  density  of  the  urine 
being  determined  by  the  urinometer,  the  two  final  figures  above 
1000  are  multiplied  by  2,  and  the  number  thus  obtained,  by  the 
number  of  litres  of  urine  voided  in  twenty-four  hours.  From 
this  deduct  60,  which  represents  the  average  quantity  of  solid 
matter  other  than  sugar,  and  the  remainder  will  represent  the 


172 


THE  URINE  IN  HEALTH  AND  DISEASE. 


amount  of  sugar  in  the  volume  of  twenty  four  hours'  urine. 
Supposing  4  litres  of  urine  have  been  passed  in  twenty-four 
hours  of  a  specific  gravity  of  1036,  then  36  x  2  x  4=288  grammes, 
which  represents  the  total  solids  in  twenty-four  hours'  urine ; 
then  288 — 60=228  grammes  of  sugar,  or  57  grammes  per  litre. 
Allowance  has  to  be  made  for  temperature. 

Gerrard's  Percentage  Glycosometer.  —  This  instrument 
consists  of  a  burette  graduated  to  read  the  percentage  of  sugar, 
or  grains  per  ounce,  in  urine,  without  the 
need  of  any  calculation. 

Analysis. — Take  either  10  drachms  or 
10  c.c.  of  urine  which  is  found  to  con- 
tain sugar,  and  dilute  with  water  to  100 
drachms  or  100  c.c.  Mix  well.  Then 
introduce  10  c.c.  or  2 \  drachms  of  Feh- 
ling's  solution,  and  40  c.c.  (10  drachms)  of 
water  into  the  porcelain  dish  and  boil. 
While  the  reagent  is  boiling,  run  the  urine 
from  the  burette  into  the  dish  in  a  slow 
stream  until  the  blue  colour  of  the  '  Feh- 
ling '  has  disappeared.  The  level  of  the 
urine  in  the  burette  shows  the  percentage 
of  sugar  present,  and  the  equivalent  in 
grains  is  given  in  the  annexed  table.  As 
the  instrument  is  graduated  to  read  per- 
centages between  10  and  1  should  the 
urine  contain  more  than  10  per  cent,  of 
sugar,  dilute  10  volumes  to  200  with  water, 
,  proceed  as  before,  and  multiply  the  per- 
centage by  2.    If  the  percentage  be  less 

Yig.  36.  Gerrard's  than  1>  undiluted  urine  is  to  be  used,  and 

Percentage  Gly-     the  reading  divided  by  10. 

COSOMETER. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  173 


Table  showing  the  Percentage  equivalent  in  Grains  per 
Fluid  Ounce. 


• 

(jr£iins  per 

Gr  iins  per 

Percentage. 

Fluid  Ounce. 

Percentage. 

Fluid  Ounce. 

100  ... 

...  4375 

1-9  ... 

8.3 

9*5 

41-55 

1-8  ... 

7-9 

90 

...  394 

1-7  ... 

7-45 

8'5  ... 

...  37-2 

1-6  ... 

7-0 

8-0  ... 

...  35*0 

1-5  ... 

...  6-55 

75  ... 

..  32-8 

1-4  ... 

...  6-1 

7-0  ... 

...  30-6 

1-3  ... 

.  .  5-7 

6-5  ... 

...  28-45 

1-2  ... 

...  5-25 

6-0  ... 

...  26-25 

1-1  ... 

...  4-8 

5*5  ... 

...  24-05 

1-0  ... 

...  4-4 

5-0  ... 

...  21-9 

•9  ... 

...  3-95 

4-5  ... 

...  19-7 

•8  ... 

...  3.5 

4-0  ... 

...  17-5 

'/ 

...  3-05 

3-5  ... 

...  15-3 

•6  ... 

...  2-6 

3-0  ... 

...  13-1 

•5  ... 

...  2-2 

2'5  ... 

...  10-95 

•4  ... 

...  1-75 

2-0  ... 

...  8-75 

Optical  Quantitative  Analysis. — This  process  is  based  on 
the  property  which  sugar  possesses  of  deviating  the  plane  of 
polarization  to  the  right.  For  aqueous  solutions  of  sugar  it  is 
well  adapted,  but  not  for  urine.  As  the  result  of  numerous 
analyses  by  Worm-Miiller,  he  found  that  when  urine  contained 
more  than  5  per  cent,  of  sugar  the  polariscope  gave  lower 
figures.  This  depends,  according  to  Kutz,  on  the  fact  that  in 
grave  forms  of  diabetes  the  urine  contains  oxybutyric  acid,  which 
is  levogyrate  and  non-fermentable ;  and,  according  to  Seegen, 
the  urine  may  contain  levulose.  This  process  is  therefore  more 
suited  to  the  chemical  laboratory  than  for  the  purposes  of  the 
clinician. 

Pathological  Significance.— Sugar  exists  normally  in  the 
blood  of  man,  in  all  the  mammalia,  and  in  almost  all  the  animal 
series.  In  the  condition  of  perfect  health  it  disappears  in  the 
tissues  by  undergoing  a  process  of  oxidation,  being  thus  con- 
verted into  water  and  carbonic  acid.  The  presence  of  a  small 
quantity  of  glucose  in  the  urine  is  held  by  some  authorities 


174 


THE  URINE  IN  HEALTH  AND  DISEASE. 


to  be  quite  compatible  with  perfect  health  (physiological  glyco- 
suria), but  the  proportion,  according  to  Worm-Miiller,  does  not 
exceed  from  0*025  to  0*5  per  cent. 

According  to  Bouchard,*  glycosuria  appears  when  the  blood 
contains  more  than  from  4  to  6  grammes  of  sugar  per  kilo- 
gramme. Temporary  or  physiological  glycosuria  may  be 
occasioned  by  the  ingestion  of  large  quantities  of  sugar,  or  of 
substances  such  as  milk,  starch,  etc.,  capable  of  being  trans- 
formed into  sugar  in  the  process  of  digestion  (alimentary 
glycosuria).  Of  this  nature  is  likewise  the  glycosuria  observed 
in  females  after  child-birth,  in  females  nursing,  and  in  certain 
pregnant  females.  The  physiological  sympathy  between  the 
uterus  and  mammae  is  disturbed ;  and  notably,  when  the  secre- 
tion of  milk  is  arrested,  glycosuria  appears  ;  while,  conversely,  if 
the  secretion  of  milk  be  abundant,  it  is  rarely  found. 

Glycosuria  may  be  a  symptom  of  transient  impressions  on  the 
system  (symptomatic  and  toxic  glycosuria),  and  is  thus  found  in 
cases  of  poisoning  by  phosphorus,  arsenic,  carbonic  oxide,  curara, 
turpentine,  nitrate  of  amyl,  morphia  (in  large  doses),  chloral, 
chloroform,  alcohol,  hydrocyanic  acid,  mercury,  etc.  It  is  also 
found  co-existent  with  such  independent  diseases  as  pneumonia, 
phthisis,  yellow  atrophy  of  the  liver,  thrombosis  of  the  portal 
vein,  chronic  gastritis,  malaria,  cerebral  tumours,  and  haemor- 
rhage, lesions  of  the  brain  and  spinal  column,  psychical  hyper- 
excitation,  etc.  These  several  conditions  resolve  themselves 
finally  into  impressions  on  the  nervous  system,  some  ill-defined 
aberrant  condition  being  the  primary  factor  in  their  causation. 

Idiopathic  Glycosuria. — The  most  prominent  feature  of  this 
condition  is  polyuria,  with  progressive  emaciation.  While 
emaciation  is  the  rule,  exceptional  cases  are  sometimes  en- 
countered in  which  the  patient  does  not  lose  much  flesh,  when, 
indeed,  a  certain  amount  of  embonpoint  exists.  In  these  cases 
it  is  found  that  the  amount  of  urea  in  the  urine  is  diminished, 
while  in  the  former  it  is  much  increased.  In  such  cases  Garrod 
has  found  as  much  as  70  grammes  of  urea  in  the  daily  excretion 
of  urine,  with  226*46  grammes  of  sugar. 

*  Maladies  par  Reltntissement  de  la  Nutrition,  2nd  edition,  Pari?, 
1885. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  175 


Diabetic  urine,  in  addition  to  being  abundant,  is  usually  of  a 
pale  straw-colour,  of  a  saccharine  odour,  often  compared  to  the 
smell  of  violets,  musk,  etc.,  and  of  a  high  specific  gravity,  as  a 
rule  ranging  from  1025  to  1050.  When  the  quantity  of  sugar 
is  less  abundant,  the  specific  gravity  may  descend  to  1010. 
Uric  acid  and  earthy  phosphates  are  sometimes  found  in 
saccharine  urine.  After  the  lapse  of  from  two  to  three  days 
such  urine  undergoes  fermentation,  and  is  found  to  contain  the 
Penicillium  glaucum,  and  spores  analogous  to  the  ferment  of 
beer,  which  decompose  the  sugar  into  alcohol  and  carbonic  acid. 
On  the  drying  of  clothes  which  may  have  been  saturated  with 
saccharine  urine,  a  white  powdery  deposit  is  left,  which  is  often 
the  first  thing  to  attract  the  attention  of  the  patient. 

The  amount  of  glucose  contained  in  the  daily  discharge  of 
urine  varies  from  80  to  100  grammes  on  an  average.  Jaccond 
places  it  as  high  as  500  grammes,  while  in  exceptional  cases  it 
reaches  the  high  figure  of  1,200  to  1,375  grammes  (Lecorche, 
Fereol).  The  proportion  of  glucose  is  found  to  vary  in  the  same 
individual  according  to  the  time  at  which  it  is  excreted ;  thus, 
the  urine  of  the  day  contains  more  (muscular  exertion  no  doubt 
contributing  to  this)  than  that  of  the  night.  In  advanced 
diabetes  the  reverse  is  the  case.  Glucose  reaches  its  maximum 
in  the  urine  after  food,  and  especially  so  if  starchy  constituents 
have  been  partaken  of.  In  order  to  estimate,  therefore,  the 
amount  of  glucose,  a  specimen  of  urine  should  be  taken  from  the 
combined  amount  passed  in  twenty -four  hours. 

Nitrogenous  diet  and  abstinence  diminish  the  a.mount  of 
glucose  in  the  urine,  and  cane-sugar  and  starch  augment  it. 
Glycerine,  saccharine,  lactose,  and  levulose  seem  to  exert  no 
influence  over  it. 

Diabetic  urine  sometimes  contains  albumen,  and  this  is 
doubtless  due  to  the  transitory  irritation  and  hyperemia,  as  in 
the  case  of  bile  and  other  substances,  which  cause  even  the 
formation  of  tube-casts.  Levulose  and  inosite  often  co-exist 
with  glucose  in  diabetic  urine,  and  occasionally  dextrine  almost 
entirely  replaces  glucose. 

Oxybutyric  acid,  acetone,  and  alcohol  may  also  be  found  in 
diabetic  urine.   Oxybutyric  acid  deviates  the  plane  of  polarization 


176  THE  UKINE  IN  HEALTH  AND  DISEASE. 

to  the  left,  and  the  error  which  may  thus  arise  should  be 
corrected  by  the  use  of  Fehling's  solution.  Chloride  of  sodium 
is  often  diminished  in  quantity  in  diabetic  urine. 

Phosphaturia,  oxaluria,  and  azoturia  may  co-exist  with,  and 
sometimes  take  the  place  of,  glycosuria. 

Therapeutic  Indications. — Glycosuria  appears  to  be  due  to 
some  obscure  disease  of  the  nervous  centres  not  yet  well  defined, 
and  death  ensues  from  debility,  progressive  wasting,  and 
exhaustion.  Consequently  tonic  treatment  is  indicated — iron, 
strychnine,  arsenic,  and  phosphorus  may  be  administered  singly 
or  in  some  of  their  numerous  forms  of  combination,  Easton's 
syrup  being  one  of  the  best.  The  diet  should  be  chiefly  nitro- 
genous, and  all  saccharine  and  starchy  food  should  be  withheld. 
There  is  no  objection  to  the  administration  of  dry  sherry  in 
moderate  quantity.  Theoretically,  peroxide  of  hydrogen  and 
permanganate  of  potash  have  found  favour  in  the  treatment 
of  glycosuria.  Two  or  three  grains  of  codeia,  especially  in 
combination  with  about  half  a  grain  of  extract  of  belladonna, 
most  markedly  diminish  the  amount  of  the  urine  secreted,  while 
these  agents  do  not,  however,  diminish  the  specific  gravity. 
Antipyrin  is  said  to  diminish  the  amount  of  sugar. 

Simulated  Glycosuria. — For  purposes  of  deception  in  the 
case  of  hospital  patients  and  others,  glycosuria  is  not  un 
frequently  simulated  by  the  addition  of  cane-sugar  to  the  urine. 
This  fraud  is  easily  detected,  as  such  urine  does  not  reduce 
Fehling's  solution.  The  cane-sugar  is  usually  added  in  excess, 
and  the  density  of  the  urine  is  thus  suspiciously  increased  (1070 
and  beyond).  By  heating  this  urine  for  a  few  minutes  with  a 
dilute  acid,  the  cane  is  transformed  into  grape  sugar,  and  Feh- 
ling's test  may  be  applied.  Again,  the  saccharimeter  in  the 
former  case  shows  a  right  deviation,  while  the  latter  is  levc- 
gyrate. 

Sometimes  grape-sugar  (raisin)  is  added.  In  this  case  the 
fraud  is  more  difficult  of  detection.  Grape-sugar  as  existing  in 
commerce  is  never  chemically  pure,  and  contains  products  inter- 
mediate between  grape-sugar  and  dextrine,  possessing  a  right 
rotation.  In  a  case  of  genuine  glycosuria,  the  results  obtained 
by  chemical  and  optical  analysis  vary  but  to  a  trifling  degree, 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  177 


while  if  grape-sugar  has  been  added  to  the  urine,  the  chemical 
method  gives  a  higher  result  than  the  optical. 

LEVULOSE,  LACTOSE,  INOSITE. 

Levulose,  or  Invert  Sugar  (C6H1206),  is  sometimes  found 
in  the  urine  of  diabetic  patients.  Its  behaviour  with  reagents  is 
almost  identical  with  that  of  glucose.  It  is  uncrystallizable,  and 
deviates  the  plane  of  polarization  to  the  left.  It  undergoes 
fermentation,  but  less  readily  than  glucose.  A  saccharine  urine 
with  left  rotation  usually  points  to  levulose.  It  must  be  borne 
in  mind  in  this  connection  that  the  ingestion  of  chloral,  camphor, 
and  benzene  gives  to  the  urine  a  like  property,  while  it  reduces 
copper  in  alkaline  solutions.  Levulose  is  also  indicated  when 
Fehling's  solution  shows  a  greater  proportion  of  sugar  than 
polarization  does. 

Lactose,  or  Sugar  of  Milk  (Saccharum  Lactis,  B.P. — 
C12H22O11),  as  already  noted,  usually  exists  in  the  urine  of 
pregnant  and  nursing  females,  and  children  at  the  breast.  It  is 
the  sweet  principle  of  the  milk  of  animals,  and  does  not  undergo 
the  alcoholic  or  vinous  fermentation.  It  crystallizes  in  oblique 
prisms,  soluble  in  water,  but  insoluble  in  alcohol  and  ether.  Its 
solutions  are  dextrogyrate.  It 
resembles  grape-sugar  in  reducing 
alkaline  solutions  of  copper  with 
precipitation  of  suboxide,  but  it 
has  no  effect  on  Barfoed's  re- 
agent.* In  order  to  prove  its 
presence  in  urine  it  must  be  sepa- 
rated in  the  following  manner  : 
The  urine  is  precipitated  by  a 
mixed  solution  of  acetate  of  lead  37.— Lactose. 
and  ammonia.  The  precipitate  obtained  is  decomposed  by 
sulphuretted  hydrogen,  and  the  hydrochloric  acid  liberated  is 
neutralized  by  oxide  of  silver.  After  nitration  the  excess  of 
silver  is  precipitated  by  carbonate  of  baryta.  A  crystalline  mass 
is  obtained  by  further  filtration  and  concentration,  which  can  be 

*  A  weak  solution  of  acetate  of  copper  with  1  per  cent,  of  acetic 
acid. 

12 


178 


THE  URINE  IN  HEALTH  AND  DISEASE. 


crystallized  after  washing  with  dilute  alcohol.  It  is  distinguished, 
as  already  indicated,  by  reducing  4  Fehling,'  and  having  no 
influence  on  Barfoed's  reagent. 

Inosite  (C6H1206+2H20). — This  substance  is  isomeric  with 
glucose,  and  is  found  in  the  muscles,  in  the  lungs,  in  the  kidneys, 
liver,  brain,  etc.    It  sometimes  co-exists  with  glucose  in  the 


light.  It  is  precipitated  by  basic  acetate  of  lead.  If  a  solution 
of  inosite  with  nitric  acid  be  evaporated  to  dryness  on  a  platinum 
plate,  the  residue  moistened  with  a  little  chloride  of  ammonium 
and  chloride  of  lime,  and  carefully  again  evaporated,  a  beautiful 
rose  coloration  is  produced  (Scherer). 

Mercuric  nitrate  solution  gives  with  neutral  solutions  of 
inosite  a  yellow  precipitate.  By  carefully  evaporating  the  liquid 
the  precipitate  becomes  more  or  less  red,  the  colour  disappearing 
on  cooling.  As  albumen  behaves  similarly,  care  should  be  taken 
that  the  urine  contains  none  of  it.  If  sugar  be  present,  the 
coloration  is  black ;  it  also  must  be  removed. 

Analysis. — The  urine  is  treated  by  neutral  acetate  of  lead, 
which  separates  the  sulphates,  chlorides,  etc.,  boiled  and  filtered. 
The  filtered  liquid  is  then  evaporated  to  about  a  fourth ;  basic 
acetate  of  lead  is  again  added,  and  a  precipitate  is  obtained 
containing  inosite.  This  precipitate  is  collected,  washed  with 
distilled  water,  then  suspended  in  a  fresh  quantity  of  water,  and 


Fig.  38. — Inosite. 


urine.  It  crystallizes  in  a 
rhomboidal  form  or  pris- 
matic needles.  It  is  very 
soluble  in  water,  but  is  in- 
soluble in  ether  or  absolute 
alcohol.  It  does  not  under- 
go alcoholic  fermentation, 
but  in  contact  with  proteid 
animal  matter  it  is  con- 
verted into  lactic  and  buty- 
ric acid.  It  does  not  become 
brown  on  boiling  with  liquor 
potassae,  it  does  not  reduce 
Fehling's  solution,  and  is 
without  action  on  polarized 


ABNORMAL  CONSTITUENTS  OF  THE  URINE. 


179 


decomposed  by  sulphuretted  hydrogen.  The  resulting  sulphide 
of  lead  is  separated  by  filtration,  the  filtered  fluid  is  concentrated 
by  evaporation,  and  the  inosite  precipitated  by  the  addition  of 
concentrated  alcohol.  After  repose  the  deposit  acquires  more 
or  less  coherence.  It  is  then  redissolved  in  distilled  water, 
evaporated,  a  little  concentrated  alcohol  or  ether  added,  and 
crystallization  allowed  to  take  place.  The  tests  of  Scherer  and 
Gallois  may  then  be  applied. 

Pathological  Significance.— Inosite  is  found  in  the  urine  in 
most  cases  of  polyuria.  In  thirty  cases  of  diabetes  and  twenty- 
five  of  albuminuria,  Gallois  found  inosite  in  seven — viz.,  in  five 
of  the  former  and  two  of  the  latter. 


o 


Cystine. 

Cystine  (C6H6NS204),  first  discovered  by  Wollaston  in  1810 
is  sometimes  found  in  a  state  of  solu- 
tion in  the  urine.  It  is  most  frequently 
found  in  a  sedimentary  form,  often  in 
combination  with  urate  of  soda,  and  in 
the  majority  of  cases  in  the  form  of  a 
calculus.  Cystine  is  found  in  the  sub-  > 
stance  of  the  liver  and  kidneys.    It  is  a  O  ^ 

remarkable  fact  that  it  is  sometimes     Fig.  39. — Cystine. 
found  in  several  members  of  the  same  family,  so  as  to  constitute 
a  distinct  diathesis  allied  to  the  rheumatic. 

Characters  and  Properties. — Cystine  is  a  substance  rich  in 
nitrogen  and  sulphur.  It  is  colourless,  inodorous,  and  entirely 
transparent,  and  crystallizes  in  hexagonal  scales.  It  is  insoluble 
in  water,  alcohol,  and  ether,  but  readily  soluble  in  ammonia, 
unlike  the  somewhat  similar  crystals  of  uric  acid.  It  is  likewise 
soluble  in  solutions  of  potash,  the  mineral  acids,  and  oxalic  acid, 
but  insoluble  in  tartaric  and  citric  acids.  Heated  on  platinum 
it  decomposes,  evolving  a  foetid  odour,  and  burns  with  a  greenish- 
blue  flame  ;  heated  on  silver  it  causes  a  black  or  brownish  stain 
of  sulphide  of  silver.  Cystine  dissolves  with  the  aid  of  heat  in 
nitric  acid ;  on  the  solution  being  evaporated,  a  reddish  residue  is 
left,  which  is  not  affected  by  caustic  alkalies. 

The  presence  of  sulphur  in  cystine  can  be  demonstrated  by 


180  THE  URINE  IN  HEALTH  AND  DISEASE. 


solution  in  caustic  soda,  boiling  for  a  few  minutes,  and  adding  a 
solution  of  oxide  of  lead :  a  black  precipitate  of  sulphide  of  lead  is 
obtained.  The  presence  of  nitrogen  is  shown  by  heating  in  a 
tube  with  a  fragment  of  potash,  when  ammonia  is  evolved. 

If  cystine  be  dissolved  in  a  strong  solution  of  boiling  potash, 
and  a  weak  solution  of  nitro-prussiate  of  soda  be  added,  a  beauti- 
ful violet  colour  results.  Urine  containing  cystine  is  characterized 
by  its  pale  colour,  tendency  to  alkalinity,  and,  during  putrefac- 
tion, by  the  exhalation  of  an  odour  of  sulphuretted  hydrogen.  If 
it  contain  much  cystine  the  specific  gravity  is  high. 

Analysis. — To  separate  cystine  dissolved  in  urine  it  is  precipi- 
tated by  acetic  acid ;  the  precipitate  is  collected  on  a  filter,  and 
dissolved  by  means  of  ammonia.  By  evaporation  of  the 
ammoniacal  solution,  or  the  addition  of  acetic  acid,  the  cystine 
crystallizes  in  characteristic  hexagonal  scales,  when  the  tests 
above  mentioned  may  be  applied. 

Tyrosine  and  Leucine. 

Tyrosine  (C9HnN03) 
and  leucine  are  products 
of  imperfect  oxidation 
of  albuminoid  sub  - 
stances.*  Both  bodies 
are  found  normally  in 
the  liver,  pancreas, 
lymphatic  glands,  etc., 
and  wherever  albumi- 
nous substances  under- 
go putrefaction,  as  in 
old  cheese. 

Properties.  —  Tyro- 
sine is  sparingly  soluble 
in  cold  water ;  it  dis- 
solves in  150  parts  of 
boiling  water,   and  is 
insoluble  in  ether.  It 
is    difficult   of  solution  in   pure   alcohol,    but   dissolves  in 
ammoniacal  alcohol,  in  acids,  and  caustic  alkalies  and  carbonates. 
*  Vide  *  Lectures  on  Bright's  Disease,'  by  Author,  p.  63. 


Fig.  40. — Tyrosine. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  181 


It  does  not  sublime  when  heated,  being  thus  distinguished  from 
leucine,  and  decomposes  with  an  odour  of  burnt  horn.  It 
crystallizes  in  the  form  of  elongated  silky  needles,  uniting  in 
radiate  form  (Fig.  40). 

Evaporated  on  a  platinum  plate,  it  assumes  an  orange  colour, 
and  leaves  a  deep  yellow  residue,  transformed  into  red  by  soda. 
Evaporated  anew,  the  liquid  becomes  brownish -black  (Scherer's 
reaction).  If  nitrate  of  mercury  be  added  to  a  boiling  solution 
of  tyrosine,  a  flaky  red  precipitate  is  obtained,  and  the  solution 
assumes  a  rose  colour.  If  a  few  drops  of  tyrosine  be  mixed  with 
a  few  drops  of  concentrated  sulphuric  acid  in  a  capsule,  gently 
heated,  and  a  little  water  be  added,  a  liquid  is  obtained  which, 
neutralized  with  carbonate  of  baryta,  gives  with  neutral  per- 
chloride  of  iron  a  beautiful  violet-red  coloration. 

Pathological  Significance.  —  Tyrosine  does  not  exist  in 
healthy  urine.  With  leucine,  it  is  found  in  the  urine  in  cases  of 
yellow  atrophy  of  the  liver,  typhus  fever,  and  small-pox,  and  in 
cases  of  poisoning  by  phosphorus,  where  the  blood  is  sub- 
oxidized.  In  pernicious  anaemia  it  has  also  been  found,  and 
here  there  is  likewise 
sub  oxidation  from  a 
deficiency  of  red  cor- 
puscles. Microscopic 
examination  most 
easily  reveals  the  pre- 
sence of  tyrosine  and 
leucine. 

Leucine  (C6H13N02), 
like  tyrosine,  is  derived 
from  organic  constitu- 
ents rich  in  nitrogen. 
It  is  found,  in  like 
manner,  normally  in 
the  liver,  pancreas  and 
spleen. 

Properties.  —  Pure 
leucine  crystallizes  in  the  form  of  successive  thin  plates.  When 
impure,  as  found  in  clinical  research,  it  presents  the  form  of 


Fig.  41. — Leucine. 


182  THE  UBINE  IN  HEALTH  AND  DISEASE. 


small  spherules,  usually  coloured,  striated,  and  with  jagged 
projections.  Gently  heated  to  170°,  it  sublimes  in  a  flaky 
cloud,  and  is  thus  distinguished  from  tyrosine.  If  the  tem- 
perature be  elevated  to  180°,  the  leucine  is  decomposed,  leaving 
a  liquid  from  which  amylamine  (C10H13N)  crystallizes  out  on 
cooling.  Evaporated  on  a  platinum  plate  with  nitric  acid, 
leucine  leaves  a  spare,  colourless  residue,  which,  treated  with 
a  few  drops  of  caustic  soda,  dissolves  on  being  heated,  giving  a 
colourless  or  yellow  fluid,  which,  again,  on  evaporation,  forms  an 
oily  globule,  which  rolls  about,  and  does  not  tarnish  the  platinum. 

Pathological  Significance. — Leucine  exists  in  the  urine  in 
cases  of  yellow  atrophy  of  the  liver. 

Analysis. — Tyrosine  and  leucine  are  usually  found  in  the 
urine  in  the  state  of  solution.  Leucine  is  always  in  smaller 
quantity  than  tyrosine.  To  separate  these  constituents  from  the 
urine,  if  it  be  albuminous,  the  albumen  must  first  be  removed  by 
coagulation  and  filtration.  The  filtrate  is  then  precipitated  by 
basic  acetate  of  lead.  This  is  again  filtered,  and  the  excess  of 
lead  removed  by  a  current  of  sulphuretted  hydrogen.  Filtration 
is  again  resorted  to,  and  the  filtrate  evaporated.  After  a  brief 
repose  tyrosine  deposits.  This  deposit  may  again  be  dissolved 
in  boiling  water,  allowed  to  crystallize,  and  examined  micro- 
scopically, or  with  the  above-mentioned  reagents. 

To  separate  leucine,  the  fluid  from  which  the  tyrosine  has 
been  obtained  is  evaporated  to  dryness,  treated  at  first  with  cold 
and  then  with  boiling  alcohol.  The  alcoholic  solution  thus 
obtained  is  evaporated  to  a  syrupy  consistence,  and  after  a  short 
time's  repose  the  leucine  separates  in  its  characteristic  spherical 
form.  The  leucine  is  yet  impure,  and  should  be  purified  as 
follows  before  applying  chemical  tests  :  Dry  the  leucine  between 
two  sheets  of  filter  paper,  dissolve  in  ammoniacal  solution, 
and  precipitate  the  solution  by  neutral  acetate  of  lead.  Filter  ; 
suspend  the  precipitate  in  water,  and  decompose  by  sulphuretted 
hydrogen.  Concentrate  the  filtered  fluid  by  evaporation,  and  set 
aside  for  crystallization.  In  the  form  of  a  sediment  tyrosine  is 
recognised  in  the  following  manner :  The  sediment  is  collected 
on  a  filter,  washed  with  water,  and  dissolved  in  ammonia  with 
the  addition  of  a  little  carbonate  of  ammonia.  Crystallize  by 
evaporation,  and  examine  microscopically  and  chemically. 


ABNOBMAL  CONSTITUENTS  OF  THE  URINE.  183 


ACETONE. 

History  of  Acetone — Properties — ChautarcTs  Test — Orthonitrobenzal- 
dehyde  Reaction  —Extraction  of  Acetone  from  Urine — Quantitative 
Analysis — Pathological  Significance — Various  forms  of  Acetonuria. 

Acetone  (C3H60)  is  often  found  in  diabetic  urine  (acetonuria), 
being  first  discovered  in  this  fluid  by  Peters.*  It  is  most  usually 
found  in  the  urine  in  the  advanced  stages  of  diabetes.  It  is  also 
found  in  a  considerable  number  of  febrile  affections,  as  in 
scarlatina,  pneumonia,  and  cancerous  affections  of  the  digestive 
organs ;  and  in  leucocythaemia,  pernicious  anaemia,  Addison's 
disease,  etc.  Urine  containing  acetone  emits  a  peculiar  odour 
like  that  of  chloroform,  is  usually  scanty,  and  of  high  specific 
gravity.  In  proportion  to  the  abundance  of  acetone,  that  of 
glucose  is  inversely  diminished.  The  breath  also  has  the 
characteristic  smell  of  acetone,  especially  in  the  last  stages  of 
diabetes.  According  to  Jaksch,  acetone  exists  in  feeble  quantity 
in  normal  urine  (0*01  or  more  in  twenty-four  hours). 

Properties. — Acetone  is  a  clear  liquid  of  a  density  of  0*814, 
boiling  at  56°  C,  inflammable,  and  of  an  agreeable  odour  (like 
acetic  ether),  and  mixes  in  all  proportions  with  alcohol  and  ether. 
Submitted  to  the  successive  influence  of  a  concentrated  solution 
of  iodine  in  iodide  of  potassium  and  of  caustic  soda,  it  forms  iodo- 
form, which  separates  in  microscopic  hexagonal  tablets,  or  in 
stars  of  six  arms,  of  a  yellow  colour  and  disagreeable  odour 
(Lieben's  reaction).  Alcohol,  according  to  Jaksch,  gives  the 
same  reaction,  but  with  it  the  iodoform  forms  much  less  rapidly 
than  with  the  acetone. 

Acetone  may  be  obtained  by  the  distillation  of  acetate  of  soda, 
or  a  mixture  of  acetate  of  lead  and  of  lime.  The  condensed 
liquid  is  brought  under  the  action  of  chloride  of  lime,  and  then 
distilled  on  a  water-bath.  The  distillate  is  collected.  This  is 
again  brought  in  contact  for  several  hours  with  lime,  then  dis- 
tilled anew,  collecting  only  what  passes  at  56°  C.  Acetone  com- 
bines with  bisulphite  of  soda,  forming  a  crystalline  compound. 

In  1864  Gerhardtf  demonstrated  that  certain  urines  containing 

*  Vierteljahrschrift  fur  de  Pract.  HeilJcunde,  Prague,  1857. 
f  Gerhardt,  Wiener  Medicinische  Presse,  vol.  iv.,  p.  28. 


184 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


sugar  were  coloured  red  by  the  addition  of  perchloride  of  iron. 
Until  recently  it  was  believed  that  this  coloration  was  due  to 
the  acetone  contained  in  the  urine  ;  and  certain  of  the  phenomena 
of  the  comatose  state,  in  cases  of  diabetes,  were  attributed  to  this 
principle.  Von  Jaksch  subsequently  arrived  at  different  con- 
clusions from  Gerhardt,  and  he  proved  that  the  reaction  described 
by  Gerhardt  was  produced  by  acetylacetic  acid,  while  with  re- 
gard to  the  acetone,  it  was  necessary  for  its  detection  to  employ 
a  special  method.  Urine  containing  sulphocyanide  of  potassium 
is  also  coloured  red  by  perchloride  of  iron. 

The  reddish-brown  colour  produced  by  sulphuric  acid  in  urine 
containing  acetone  is  also  equally  fallacious,  as  it  is  likewise  pro- 
duced in  urines  which  do  not  contain  this  principle.  The  same 
applies  to  the  reaction  of  Lieben.  The  following  tests  are,  how- 
ever, reliable. 

Chautard's  Test.* — Dissolve  0*25  gramme  of  fuchsine  in 
500  grammes  of  water,  through  which  pass  a  current  of  sul- 
phurous acid  until  the  yellow  colour  disappears.  This  solution 
(sulpho-rosanilinic  reaction)  may  be  kept  indefinitely  in  stoppered 
bottles.  With  a  tenth  part  of  acetone,  this  reagent  gives  an 
intense  violet  colour,  with  4^th  a  similar  colour,  and  with  iTnnrth 
a  sufficiently  appreciable  colour.  When  the  amount  of  acetone  is 
small,  200  c.c.  of  the  urine  may  be  distilled,  and  the  first  15  c.c. 
of  the  distillate  may  be  tested. 

Orthonitrobenzaldehyde  Reaction.  —  This  test,  of  great 
sensibility,  has  been  recommended  by  Baeyer  and  Drewsen.  A 
few  crystals  of  orthonitrobenzaldehyde,  which,  being  explosive, 
must  be  carefully  handled,  are  boiled  with  a  little  water,  and  the 
solution  allowed  to  cool.  To  the  first  products  of  the  distillation 
of  the  urine,  rendered  alkaline  with  a  soda  solution,  some  of  the 
above  solution  is  added.  After  about  six  minutes,  if  the  urine 
contain  acetone  it  becomes  yellow,  then  green,  and  finally  pre- 
cipitates indigo.  If  the  acetone  be  only  in  small  quantity,  the 
yellow  fluid  is  to  be  agitated  with  chloroform,  and  after  a  short 
time  the  indigo  colour  ensues. 

Otherwise,  prepare  ready  for  use  a  5  per  cent,  solution  of 
nitro-prussiate  of  soda  and  a  30  per  cent,  solution  of  caustic 
*  Bu'letin  de  la  Socie'U  Ghimique,  t.  45. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  185 

potash.  To  the  first  portion  of  the  distillate  a  few  drops  of 
each  of  these  solutions  are  added ;  boil,  and  add  a  few  drops  of 
acetic  acid  by  pouring  gently  along  the  tube  wall  so  as  to  prevent 
admixture.  At  the  point  of  junction  of  the  fluids  a  beautiful  red 
colour  is  produced.  The  successive  addition  of  the  foregoing 
solutions  even  without  acetic  acid  causes  a  pronounced  red 
colour  with  acetone.  If  then  acetic  acid  be  added  and  the  fluid 
boiled,  the  red  colour  is  changed  into  green.  According  to 
Weyl,  creatinine  gives  the  same  reaction.* 

To  extract  Acetone  from  the  Urine. — Von  Jaksch  recom- 
mends that  almost  a  litre  of  this  fluid  should  be  acidulated  with 
hydrochloric  or  tartaric  acid,  ether  added  and  distilled.  The 
acidulation  prevents  cloudiness,  and  the  passing  of  carbonate 
of  ammonia  into  the  distillate.  To  the  latter  is  added  a  small 
quantity  of  iodine,  dissolved  by  means  of  iodide  of  potassium, 
and  finally  caustic  potash.  The  result  is,  according  to  the 
amount  of  acetone,  either  a  precipitate  or  an  opacity  due  to  the 
formation  of  iodoform  (Lieben's  reaction).  Iodoform  is  recog- 
nised by  its  odour,  by  its  volatilization  on  being  heated,  and  by 
its  crystalline  form.  In  order  to  obtain  it  in  this  form  the 
liquid  containing  the  iodoform  is  agitated  with  ether,  which 
spontaneously  evaporates,  and  the  crystals  subside. 

Quantitative  Analysis  of  Acetone.  —  Salkowskif  and 
Taniguti  employ  the  following  process  :  To  300  c.c.  of  urine  add 
10  c.c.  of  concentrated  sulphuric  acid,  and  distil.  To  the 
distillate  add  soda  or  potash  lye,  then  the  iodine  solution,  and 
set  aside  for  twenty-four  hours.  Filter,  collect  the  iodoform, 
and  weigh.  J 

Pathological  Significance. — It  has  been  observed  that  the 
breath  of  diabetic  patients  is  characterized  by  a  vinous  odour. 
This  has  in  recent  years  been  proved  to  be  due  to  the  presence 
of  acetone  (acetonemia)  in  the  blood.  According  to  Lieben,§ 
acetone  exists  to  the  extent  of  about  1  centigramme  in  the  urine 
of  twenty-four  hours  ;  but  in  certain  pathological  states  the 

*  Acetone  reduces  Fehling's  Solution. 

f  Zeit.fur  Physiol.  Chemie,  xiv.,  1890,  Heft  5. 

J  Vide  Annal.  des  Mai.  des  Organ.  Genito-Urin.,  No.  9,  1892. 

§  Lieben,  Annates  der  Chemie  und  Pharmacie,  p.  236,  1870. 


186  THE  UBINE  IN  HEALTH  AND  DISEASE. 

quantity  amounts  to  as  much  as  50  centigrammes  per  diem. 
This  pathological  condition,  to  which  the  name  of  hyper- 
acetonuria  has  been  given,  was  observed  under  four  different 
conditions :  First,  fever,  from  whatever  cause ;  secondly,  in 
diabetes ;  thirdly,  in  certain  cases  of  cancer ;  fourthly,  in 
patients  suffering  from  an  affection  to  which  Kaulich  and 
Cantani  gave  the  name  acetonemia. 

First  Form. — If  in  any  patient  the  fever  attains  to  a  high 
degree,  hyper-acetonuria  appears.  The  most  varied  affections 
present  this  phenomenon. 

Second  Form. — Independently  of  numerous  cases  of  diabetes 
in  which  acetone  is  not  in  excess,  there  are  two  varieties  :  First, 
the  cases  in  which  acetone  is  in  excess ;  secondly,  the  cases  in 
which  acetone  is  in  excess,  and  in  which  the  urine  gives 
Gerhardt's  reaction.  In  these  cases  the  affection  is  grave,  and 
death  is  usually  ushered  in  by  coma. 

Third  Form. — Acetonuria  occurs  in  certain  cases  of  carcinoma. 
The  cause  is  unknown. 

Fourth  Form. — In  the  acetonuria  of  Kaulich  and  Cantani 
acetone  is  found  in  excess  in  the  urine.  Perchloride  of  iron  in 
these  cases  invariably  gives  a  red  reaction.  Gerhardt's  reaction 
is  seldom  given  in  grave  diabetic  acetonuria.  Acetone  and 
acetylacetic  acid  are  far  from  being  independent  in  every  case. 
Siefert*  believes  that  the  appearance  of  acetone  in  the  urine  is 
due  to  the  ingestion  of  alcohol.  Like  Jaksch,  he  observed  the 
reaction  in  various  febrile  disorders,  and  distinguished  certain 
new  features  of  it,  differentiating  it  from  other  reactions  of  a 
similar  kind.  The  constituent  thus  discovered  in  the  urine 
would  be,  according  to  this  authority,  not  acetylacetic  acid,  but 
acetylacetate  of  ethyl,  which  in  decomposing  gives  origin  to 
acetone,  the  accumulation  of  this  substance  in  considerable 
quantity  in  the  organism  exercising,  according  to  Siefert,  a 
depressing  action  on  the  cerebral  functions. 

Brieger  has  demonstrated  that  it  required  at  least  2  grammes 
of  acetylacetate  of  ethyl  to  a  litre  of  urine  to  obtain  the  reaction 
of  Gerhardt.    In  another  series  of  experiments,  20  grammes  of 

*  Physikalisch- Medicinhche  Getsellschaft,  Wurzburg,  vol.  xvii., 
No.  4,  i882. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  187 


acetylacetate  of  ethyl  per  diem  were  given  to  perfectly  healthy 
men  and  to  a  diabetic  patient  without  Gerhardt's  reaction  having 
been  obtained.* 

Melanine. 

In  certain  cases  of  melanosis  this  pigment  appears  in  the 
urine,  which  when  emitted  is  clear,  but  gradually  becomes  of  a 
deep  brown,  or  even  black,  colour. 

Ordinarily  melanine  exists  in  solution  in  the  urine,  but  some- 
times in  the  form  of  a  brownish  or  black  sediment,  recognisable 
by  microscopic  examination.  Melanine  may  possess  a  diagnostic 
significance,  when  the  melanosis  is  beyond  the  reach  of  examina- 
tion by  eye  or  touch.  It  may  disappear  from  the  urine  when 
the  disease  is  arrested,  or  remain  stationary.  Oxidizing  agents, 
such  as  chromic  acid  and  fuming  nitric  acid,  transform  the 
principle  melanine,  causing  gradually  with  the  first  and  imme- 
diately with  the  second  a  black  coloration.  According  to 
Zeller,  the  most  delicate  test  for  melanine  is  bromine  water. 
With  melanine  it  gives  at  first  a  yellow  precipitate,  which 
gradually  blackens.  Urobiline  gives  a  yellow  precipitate  with 
same  reagent,  but  it  does  not  blacken. 

Diverse  Acids. 
The  following  acids  are  occasionally  found  in  the  urine  : 
Lactic  Acid  (C3H603)  is  found  in  the  urine  in  cases  of 
poisoning  by  phosphorus,  yellow  atrophy  of  the  liver,  and 
mollities  ossium.  It  is  probably  derived  from  the  fermentation 
of  saccharine  and  amylaceous  substances.  Formic  Acid 
(HCH0.2),  so  called  from  the  fact  that  it  is  ejected  from  the  red 
ant  when  irritated,  is  found  in  the  urine  in  cases  of  leucocy- 
thaemia.  Valerianic  Acid  (HC5H902)  is  found  in  the  urine  in 
cases  of  typhus  fever,  small-pox,  and  yellow  atrophy  of  the 
liver.  Acetic  (HC2H302)  and  Propionic  Acid  (C2H5COOH)  are 
found  in  cases  of  diabetes  after  the  urine  has  undergone  fer- 
mentation. Lehmann  found  Butyric  Acid  (HC4H702)  in  the 
urine  of  females  after  childbirth. 

*  Vide  1  Considerationes  sur  le  diabete  Acetonemique,'  par  J.  Cor- 
nillon  et  A.  Mallat  {Le  Progres  Medical,  April,  1886). 


188 


THE  URINE  IN  HEALTH  AND  DISEASE. 


BILE  ELEMENTS. 

Bile  Elements — Mucine  of  Bile — Biliary  Pigments  :  Bilirubine,  Bili- 
verdine,  Biliprasine,  Bilifuscine,  Bilihumine — Detection  of  Colouring 
Matter  of  Bile  in  Urine— Gmelin's  Reaction — Analysis — Rosen- 
bach's  Modification  of  Gmelin's  Test—  Huppert's  Reaction — Bile 
Acids  :  Choleic  or  Taurocholic  Acid,  Glycocholic  Acid,  Cholalic  Acid 
— Reaction  of  Bile  Acids  (Pettenkofer's  Reaction) — Cholesterine — 
— A nalysis — Pathological  Significance. 

When  secreted  by  the  liver  bile  is  a  yellow  fluid,  of  a  density 
varying  from  1020  to  1035.  According  to  the  length  of  time 
which  it  remains  in  the  gall-bladder,  it  becomes  of  a  deeper 
brown  colour.  It  contains  no  albumen.  On  being  treated  with 
alcohol,  the  mucine  which  it  contains  is  precipitated.  Of  all  the 
fluids  of  the  system  it  is  the  densest,  a  tenth  of  its  weight  consist- 
ing of  solid  matter — chiefly  biliary  pigments,  acids,  mucine,  and 
cholesterine. 

Mucine  of  Bile. — In  addition  to  its  acting  as  a  reservoir  for 
bile,  the  gall-bladder  adds  to  the  bile  its  special  secretion — 
mucine.  Bile  as  it  exists  in  the  hepatic  canals  does  not,  there- 
fore, contain  mucine.  This  constituent  may  be  separated  from 
bile  by  treating  it  with  four  or  five  times  its  volume  of  alcohol. 

Biliary  Pigments. — The  colouring  pigments  of  the  bile  are : 

Bilirubine  (Ci6H18N203). 

Biliverdine  (C16H18N204). 

Biliprasine  (CiGH22N20G) . 

Bilifuscine  (C16H2oN204). 

Bilihumine. — Atomic  composition  not  yet  determined. 

All  the  four  latter  of  this  group  of  substances  appear  to  be 
derived  from  the  former  by  oxidation. 

Bilirubine  (C16H18N203)  is  found  in  the  bile  in  small  quantity 
in  combination  with  alkaline  bases.  It  is  almost  the  sole 
constituent  of  certain  biliary  calculi.  It  may  be  removed  from 
bile  or  bilious  urine  by  the  addition  of  hydrochloric  acid  and 
agitation  with  chloroform.  It  may  be  obtained  from  calculi 
containing  it  by  first  treating  them  with  ether  to  remove 
the  fatty  matter  and  cholesterine  which  they  contain ;  the 
salts  are  then  dissolved  out  by  boiling  water,  and  the  residue 
treated  with  hydrochloric  acid  and  chloroform,  in  which  the 


ABNOKMAL  CONSTITUENTS  OF  THE  URINE.  189 


bilirubine  is  dissolved.  This  solution  by  evaporation  deposits  an 
mpure  bilirubine.  On  this  being  treated  with  alcohol  and  ether, 
bilifuscine  and  fatty  matter' are  removed  ;  the  remainder  may 
then  be  crystallized  from  chloroform.  Bilirubine  appears  in 
the  form  of  an  amorphous 
or ange -  coloured  powder. 
Crystallized  from  the  chloro- 
form solution,  it  forms  rhom- 
boidal  microscopic  prisms. 
It  is  insoluble  in  water,  spar- 
ingly soluble  in  alcohol  and 
ether,  very  soluble  in  chloro- 
form, benzene,  and  bisulphide 
of  carbon.  The  solutions  are 
yellow,  and  are  precipitated  by  soluble  metallic  salts,  the  bili- 
rubine forming  combinations  with  the  oxides  of  the  metals, 
which  are  insoluble  in  water  and  chloroform.  Bilirubine  is 
soluble  in  caustic  alkalies,  in  which,  by  the  absorption  of  oxygen, 
it  is  converted  into  biliverdine. 

Biliverdine  (C16H18N204)  is  a  product  of  the  oxidation  of 
bilirubine.  It  may  be  obtained  by  exposure  of  an  alkaline 
solution  of  bilirubine  to  the  air  in  a  wide-mouthed  bottle,  and 
shaking  from  time  to  time.  Finally  it  transforms  into  bili- 
prasine.  When  the  green  colour  due  to  oxidation  has  ceased, 
the  solution  is  precipitated  by  hydrochloric  acid.  The  precipitate 
is  washed  with  boiling  alcohol,  which  dissolves  the  biliverdine 
alone,  from  which  it  separates  on  evaporation  as  a  greenish 
residue.  Biliverdine  is  amorphous,  of  a  deep  green  colour,  in- 
soluble in  water,  ether,  and  chloroform,  but  soluble  in  alcohol 
and  alkalies,  the  solution  being  of  a  green  colour. 

Biliprasine  (C16H22N206)  is  derived  from  biliverdine  by  the 
addition  of  two  molecules  of  water.  It  is  found  in  small 
quantity  in  biliary  calculi,  from  which  it  may  be  extracted  by 
treatment  with  water,  hydrochloric  acid,  ether,  and  chloroform, 
so  as  to  remove  the  substances  soluble  in  these  agents,  the 
biliprasine  being  left  as  a  residue.  From  this  residue  it  is 
dissolved  by  alcohol,  in  which  it  is  easily  soluble,  the  solution 
being  of  a  green  colour,  becoming  brown  by  the  addition  of 


Fig.  42. — Bilirubine. 


190 


THE  URINE  IN  HEALTH  AND  DISEASE. 


ammonia.  It  is  soluble  in  alkalies,  and  the  brown  solution  is 
converted  into  green  by  the  addition  of  acids.  It  is  insoluble  in 
water,  ether,  and  chloroform. 

Bilifuscine  (Ci6H20N2O4)  is  a  deep-brown  powder,  amorphous, 
almost  insoluble  in  water,  ether,  and  chloroform,  but  readily 
soluble  in  alcohol,  ammonia,  and  soda,  giving  a  deep-brown 
solution.  It  accompanies  bilirubine  in  biliary  calculi,  and  is 
dissolved  from  them,  or  from  bile,  when  they  are  treated  with 
chloroform  and  hydrochloric  acid.  It  separates  from  bilirubine 
on  being  treated  with  alcohol,  in  which  bilirubine,  as  we  have 
seen,  is  insoluble. 

Bilihumine,  a  constituent  found  only  in  biliary  calculi,  is  of  a 
brown  earth  {humus)  colour.  Its  composition  is  not  yet  deter- 
mined. It  remains  as  a  residue  when  biliary  calculi  have  been 
successively  treated  with  wTater,  alcohol,  ether,  chloroform,  and 
hydrochloric  acid.  It  is  therefore  insoluble  in  these  agents.  It 
is  soluble  in  caustic  soda  and  ammonia,  and  is  precipitated  from 
their  solutions  by  hydrochloric  acid. 

Other  products  of  the  oxidation  of  bilirubine,  such  as  bili- 
cyanine  or  choloverdine,  and  choleteline  have  been  described. 

Detection  of  Colouring  Matter  of  Bile  in  the  Urine.— 
The  mere  aspect  of  bilious  urine  affords  an  indication  as  to  the 
particular  pigment  present.  Thus,  if  bilirubine  predominates, 
the  mine  is  yellow  ;  if  biliverdine,  it  is  greenish.  Such  urine 
stains  linen  or  blotting-paper  immersed  in  it,  and  on  being 
agitated  gives  a  yellow  froth.  Urine  passed  after  the  ingestion 
of  senna,  rhubarb,  and  santonine  presents  the  same  peculiarity, 
but  these  may  be  distinguished  by  their  characteristic  reactions. 

Gmelin's  Reaction. — If  to  a  solution  of  the  foregoing  con- 
stituents a  little  nitric  acid  be  added,  the  liquid  at  first  assumes 
a  green  colour,  then  blue,  subsequently  violet  and  red ;  and  at 
the  end  of  some  seconds,  if  the  acid  be  in  excess,  the  red  colour 
disappears,  and  the  liquid  becomes  yellow.  If  a  solution  of  the 
pigments  be  poured  on  nitric  acid  so  as  to  prevent  mixing  of  the 
fluids,  the  various  colours  appear  simultaneously  in  superposed 
layers,  the  green  being  uppermost.  The  green  colour  alone  is 
characteristic  of  the  bile  pigments. 

Analysis. — Urine  containing  bile  pigments  is  of  a  more  or  less 


ABNORMAL  CONSTITUENTS  OF  THE  UBINE.  191 

yellow  colour ;  or  it  may  be  brownish,  reddish-brown,  or  green, 
according  to  the  predominating  pigment.  When  the  urine  is 
yellow,  bilirubine  predominates  ;  when  it  is  green,  biliverdine. 
Linen  and  blotting-paper  are  stained  by  such  urine,  corresponding 
to  the  colour,  and  agitation  causes  a  coloured  froth.  Into  a 
conical  vessel  gently  pour  two  or  three  c.c.  of  nitric  acid  which 
has  been  more  or  less  exposed  to  air,  then,  by  means  of  a 
pipette,  place  over  it,  without  admixture,  a  little  of  the  urine. 
If  it  contain  bile  pigments,  there  will  be  produced  at  the 
point  of  contact  of  the  two  liquids  a  green  ring  of  more  or 
less  thickness,  and  below  this  violet,  red  and  yellow  rings. 
Indican  gives  with  nitric  acid  the  blue  and  red  coloration ; 
but  the  green  is  characteristic  of  bile  pigments. 

In  order  to  identify  bile  pigments  in  sediments,  such  as  urates, 
dissolve  these  sediments  in  carbonate  of  soda  and  test  as  above. 
The  presence  of  albumen  does  not  interfere  with  this  reaction,  if 
the  colouring  matter  be  not  in  very  minute  quantity. 

Rosenbach's  Modification  of  Gmelin's  Test. — Filter  a  given 
quantity  of  urine,  then  moisten  the  inner  surface  of  the  filter, 
still  moist,  with  nitric  acid.  Concentric  zones  of  green,  blue, 
violet,  and  reddish-yellow  then  appear  on  the  paper  if  bile  salts 
be  present. 

Bilious  urine  mixed  with  a  drop  of  nitrate  of  soda  solution 
and  a  little  dilute  sulphuric  acid  assumes  a  beautiful  green 
colour.  After  some  time  the  green  disappears,  and  is  replaced 
by  yellow,  without  passing  through  the  stages  of  red  and  blue. 

If  a  few  drops  of  tincture  of  iodine  be  added  to  bilious  urine, 
at  the  point  of  contact  of  the  fluids  a  beautiful  emerald- green 
colour  appears.    Bromine  water  produces  the  same  result. 

Bilirubine  may  be  isolated  from  bilious  urine  in  the  following 
manner  :  Into  a  small  flask  pour  100  c.c.  of  urine  and  10  c.c.  of 
chloroform,  and  gently  mix  the  two  liquids.  Invert  the  flask, 
still  closed,  gently  open  the  mouth  of  the  flask,  and  allow  the 
chloroform  emulsion  alone  to  pass  out,  and  apply  Gmelin's 
reaction. 

Huppert's  Reaction. — Add  to  the  urine  a  little  ammonia  and 
chloride  of  lime.  If  it  contain  bile  pigment,  a  precipitate  con- 
taining bilirubine  is  formed.    This  precipitate  may  be  separated 


192  THE  URINE  IN  HEALTH  AND  DISEASE. 


by  filtration,  washed,  and,  while  still  moist,  treated  with  strong 
alcohol  containing  sulphuric  acid.  On  being  heated  the  liquid 
will  become  of  an  emerald-green  or  greenish-blue  colour. 

Ehrlich  recommends  the  following  process  to  identify  bili- 
rubine  alone :  Mix  a  given  quantity  of  urine  with  an  equal 
volume  of  dilute  acetic  acid,  and  then  add,  drop  by  drop,  a 
solution  of  sulphodiabenzol  (one  part  of  sulphanilic  acid  in 
1,000  parts  of  water,  with  15  c.c.  of  hydrochloric  acid  and  0*1 
nitrate  of  soda).  If  the  urine  contains  bilirubine,  the  mixture 
assumes  the  violet  colour  characteristic  of  this  constituent. 
When  the  bile  pigments  are  decomposed,  exist  only  in  small 
quantity,  or  when  the  urine  contains  indican,  these  processes  are 
inapplicable.  In  such  cases  the  bile  pigment  must  be  isolated  ; 
to  effect  this  render  the  urine  alkaline  by  soda  lye,  then  mix 
with  chloride  of  barium  or  of  lime,  when  a  yellow  precipitate 
forms.  Filter,  and  boil  the  precipitate  with  alcohol  containing 
a  few  drops  of  sulphuric  acid,  when  the  liquid  assumes  a  beauti- 
ful blue  colour. 

Bile  Acids. 

According  to  Dragendorff,  biliary  acids  are  contained  in  normal 
urine  in  the  proportion  of  0*8  gramme  to  100  litres.*  These 
acids  are,  however,  most  frequently  found  in  pathological  states, 
united  to  the  bile  pigments.  The  two  acids  which  exist  in 
human  bile  under  the  form  of  soda  salts,  viz.,  choleic  or  tauro- 
cholic  acid,  and  cholic  or  glycocliolic  acid,  are  combinations  of 
a  third  acid,  cholalic  acid,  with  taurine  on  the  one  hand,  and 
glycochole  on  the  other. 

Choleic  or  Taurocholic  Acid  (C^H^NSO-j)  is  a  white  amor- 
phous powder,  soluble  in  water,  alcohol,  and  chloroform,  and 
insoluble  in  ether.  Its  solutions  are  dextrogyrate.  Boiled  with 
potash  or  hydrochloric  acid  for  some  hours,  it  is  resolved  into 
cholalic  acid  and  taurine. 

Glycocliolic  Acid  (C^H^NO^)  crystallizes  in  fine  needle- 
prisms,  which  are  colourless,  and  do  not  contain  sulphur,  by 


*  Annal.  des  Mai.  des  Organ.  Uenito-Ur'm.,  No.  8,  1892,  p.  647. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE 


193 


which  they  are  distinguished  from  choleic  acid.  It  dissolves 
with  difficulty  in  cold,  but  readily  in  boiling,  water  and  in 
alcohol.  It  is  sparingly  soluble  in  ether. 
On  boiling  with  potash  or  hydrochloric 
acid  it  is  resolved  into  cholalic  acid  and 
glycochole. 

Cholic  Acid  (C.2.iH40O5)  exists  in  the  urine 
only  in  combination  with  taurine  and  gly- 
cochole, with  which  it  forms  the  two  pre- 
ceding acids.  It  crystallizes  in  four  or 
six  sided  prisms.  It  is  insoluble  in  water, 
very  soluble  in  alcohol,  sparingly  soluble 
in  ether.  Its  solutions  are  dextrogyrate. 
Boiled  with  mineral  acids,  it  loses  water  Fig.  43. — Glycocholio 
and  is  transformed  into  dyslisine  (CoiH^Ai). 

Reaction  of  Bile  Acids  (PettenJcofer'a  Head  Ion). — This  is 
the  test  most  frequently  employed,  and  is  as  follows  :  To  a 
solution  of  the  foregoing  acids  add  a  few  drops  of  a  weak  solution 
of  sugar,  a  little  concentrated  sulphuric  acid,  and  heat  to  a 
temperature  not  exceeding  60°  C,  when  a  violet -purple  colour  is 
obtained.  Neukomm  renders  the  reaction  more  delicate  by  the 
following  procedure:  Mix  in  a  porcelain  capsule  a  solution  of 
bile-acids  with  a  drop  of  dilute  sulphuric  acid,  and  a  drop  or  two 
of  sugar  solution  ;  heat  on  a  water-bath,  when  a  beautiful  violet- 
purple  colour  appears. 

The  bile- acids  may  be  isolated  as  follows:  Evaporate  a  con- 
siderable quantity  of  urine  on  a  water-bath  almost  to  dryness. 
Then  extract  by  alcohol,  and  with  precaution  evaporate  anew. 
Dissolve  the  residue  in  a  few  drops  of  water  and  apply  Petten- 
kofer's  test.    Kthe  urine  contain  albumen  it  must  be  separated. 

Cholesterine. — The  presence  of  cholesterine  in  the  urine  is 
very  rare.  It  is  found  in  cases  of  chyluria  and  fatty  degenera- 
tion of  the  kidney,  sometimes  in  the  form  of  a  sediment,  and 
as  a  constituent  of  certain  calculi. 

Cholesterine  (C.25H43HO),  crystallizes  in  rhomboid  scales,  or  in 
the  form  of  fine  needles.  It  is  insoluble  in  water,  dilute  acids, 
alkalies,  and  cold  alcohol,  but  soluble  in  boiling  alcohol,  ether, 
and  chloroform.  It  may  be  extracted  from  gall-stones  by  boiling 

13 


194 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


alcohol,  from  which  it  deposits  on  cooling.  If  a  little  choles- 
terine  be  dissolved  in  2  c.c.  of  chloroform,  and  about  the  same 
volume  of  sulphuric  acid  be  added,  the  liquid  agitated,  and 
then  allowed  to  repose,  the  supernatant  chloroform  solution  is 
found  at  first  to  be  of  a  blood-colour,  then  cherry-red  or  purple, 
while  the  sulphuric  acid  becomes  intensely  green.  If  a  little 
of  the  chloroform  solution  be  put  in  a  porcelain  capsule,  it 
undergoes  rapid  coloration  from  blue  to  green  and  yellow. 

Analysis. — To  identify  cholesterine  in  the  urine,  agitate  with 
ether,  decant  the  fluid,  and  evaporate.    Treat  the  residue  with 


Fig.  44.— Cholesterine.  ammonia,  to  an  ethereal  solu- 
tion of  cholesterine  in  a  porcelain  capsule,  and  a  red  coloration 
is  the  result.  A  solution  of  iodine  and  a  drop  or  two  of  sul- 
phuric acid  causes  a  greenish-blue  coloration,  changing  to 
violet. 

Pathological  Significance. — When  bile  is  prevented  from 
flowing  into  the  intestines  from  any  cause  whatever,  such  as 
active  or  passive  hyperemia  of  the  liver,  as  from  alcohol, 
obliteration  of  the  biliary  canals  by  calculi,  catarrhal  inflamma- 
tion of  these  canals,  extending  to  the  lobules  of  the  liver,  inflam- 
mation of  the  gall-bladder,  its  compression  by  a  tumour,  inter- 
stitial hypertrophy,  as  in  phosphorus  -  poisoning,  oedema  of 
Glisson's  capsule,  etc.,  the  bile  is  reabsorbed,  and  passes  into  the 
circulation.  This  is  made  manifest  by  the  yellow  colour  im- 
parted to  the  various  tissues  of  the  body,  and  notably  the  con- 
junctiva. Bile  elements  are  then  eliminated  by  the  kidney,  and 
are  found  in  the  urine. 


alcohol,  add  a  little  potash,  and 
boil  for  some  time  on  a  water- 
bath.  Treat  the  residue  with 
water,  and  agitate  with  ether. 
Evaporate  the  ethereal  solution, 
redissolve  the  crystals  in  boiling 
alcohol,  filter,  and  allow  crystal- 
lization to  take  place. 


Add,  drop  by  drop,  strong 
sulphuric  acid,  or  nitric  acid  and 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  195 


Fatty  Matter. 

Lipuria,  Chyluria,  Galacturia.*— Cases  of  chyluria  may  be 
grouped  as  follows  : 

Chyluria  properly  so  called,  when  it  depends  or  not  on 
parasites.  The  parasitic  form  of  chyluria  is  found  in  tropical 
climates,  and  is  caused  by  a  round  worm,  the  Filaria  sanguinis 
hominis.  The  passing  of  the  parasite  from  the  blood  to  the 
kidney  causes  chyluria  and  hematuria.  The  urine  necessarily 
contains  albumen  in — 

Advanced  Fatty  Degeneration  of  the  Kidney,  or  of  other 
portions  of  the  urinary  tract,  as  in  cases  of  phosphorus-poison- 
ing. The  bursting  of  an  old  abscess,  and  the  consequent 
admixture  of  urine  and  pus  may  cause  chyluria. 

Phthisis,  prolonged  suppurations,  and  all  grave  constitutional 
diseases,  may  cause  chyluria. 

Chyluria  has  been  observed  after  the  ingestion  of  large 
quantities  of  aliment  rich  in  fat,  or  after  the  experimental  in- 
jection of  oil  into  the  bloodvessels.  The  fat  presents  itself  under 
the  form  of  more  or  less  voluminous  drops,  which  float  to  the 
surface  (lipuria),  or  in  a  state  of  fine  division,  as  in  milk 
(galacturia).  In  the  former  case  the  urine  appears  as  if  it  con- 
tained pus.  In  the  case  of  pus,  however,  a  deposit  takes  place, 
and  a  clear  supernatant  fluid  remains,  while  the  fatty  urine 
retains  its  opacity. 

Detection  of  Fat  in  the  Urine. — On  microscopic  examina- 
tion fat  is  observed  in  the  form  of  fine  granulations  or  small 
drops,  of  greater  or  less  size,  with  dark  contour,  a  brilliant 
centre,  and  very  refractive.  Chemically,  the  following  reactions 
take  place  with  fat :  On  being  heated,  a  characteristic  odour  of 
acrolein  is  given  off.  On  the  addition  of  chloroform  or  ether, 
or  sulphide  of  carbon,  the  urine  becomes  more  or  less  clear. 
If  the  urine  be  poured  on  white  paper,  fatty  stains  may  be 
observed.  Lecithine  and  cholesterine,  which  are  of  a  fatty 
nature,  may  also  be  found  in  the  urine. 

*  Vide  '  Annal.  des  Mai.  des  Orgs.  Genito-Urin.,'  No.  2, 1893,  p.  124. 


196  THE  URINE  IN  HEALTH  AND  DISEASE. 


Pathological  Significance. — Lipuria  most  frequently  occurs 
in  fatty  degeneration  of  the  kidney,  in  cases  of  poisoning  by 
phosphorus,  in  phthisis,  pyaemia,  gangrene,  acute  atrophy, 
and  fatty  degeneration  of  the  liver,  carcinoma,  and  prolonged 
suppurations,  especially  in  connection  with  bones  and  joints. 


By  tube-casts  are  understood  microscopic  moulds  of  the 
uriniferous  tubes  of  the  kidney,  resulting  from  inflammation  of 
the  organ.  This  inflammation  may  be  chronic  and  incurable, 
as  in  advanced  Bright's  disease,  or  may  be  due  to  transitory 


irritation  of  the  organ  from  the  elimination  of  certainirritants. 
These  casts  may  be  classified  as  :  (1)  True  cylinders  or  casts 
(cylinders  of  destruction),  comprising  the  following  granular 
cylinders,  viz.,  granular,  granulo-fatty,  fatty  and  mixed,  amyloid 
tube-casts  ;  (2)  Cylinders  of  exudation — hyaline  cylinders  ;  (3) 


Tube-Casts. 


Fig.  45.  —Fatty  De- 
generation of  Tubes 
from  the  Cortical  por- 
tion of  the  Kidney  in 
a  Case  of  Phosphorus 
Poisoning  (Phosphoric 
Steatose). — Ranvier. 


Fig.  46. — Longitudinal  Sec- 
tion of  the  Tubular  Substance 
of  the  Kidney  in  a  Case  of 
Albuminous  Nephritis  due  to 
Poisoning  by  Phosphorus. 


The  Loops  of  Henle  are  more 
altered  than  the  straight  tube  be- 
tween them. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE  197 

Cylindroids — cylindroids,  pseudo-cylinders,  epithelial  cylinders, 
hemorrhagic  cylinders,  and  spermatic  cylinders. 

Granular  Cylinders. — This  form  of  tube-casts  presents  an 
entirely  granular  aspect.  They  are  less  transparent  than  the 
amyloid  and  hyaline  casts,  and  are  generally  larger.  Some- 
times they  are  short,  and  of  considerable  diameter.  They  pre- 
sent either  a  regular  or  irregular  outline.  Their  extremities  are 
rounded,  like  the  finger-tip,  or  serrated.  They  are  composed  of 
the  debris  of  red  globules,  of  leucocytes,  and  of  epithelial  cells, 
which  have  undergone  more  or  less  degeneration. 

Granulo -fatty  cylinders  may  be  regarded  as  the  foregoing 
with  fat  globules  superadded.  They  are  found  in  Bright' s 
disease.  Pure  fatty  granules  are  found  only  in  cases  of  poison- 
ing by  phosphorus.  Mixed  cylinders  are  combinations  of 
the  foregoing. 

Amyloid  Casts  or  Cylinders.— These  cylinders  are  of  homo- 
geneous structure,  are  more  refractive  than  hyaline  cylinders, 
and  are  thus  more  denned  in  the  microscopic  field.  They 
present  a  dull,  waxy  appearance.  Ordinarily,  they  are  short, 
and  of  greater  diameter  than  the  granular  cylinders.  Their 
contour  is  regular  and  smooth  ;  sometimes  notched.  They  are 
sometimes  twisted  on  themselves  in  the  form  of  a  corkscrew. 
They  resist  the  action  of  acetic  acid,  and  are  insoluble  in  heated 
urine,  and  in  distilled  water.  Osmic  acid  imparts  to  them  a 
dark-brown  colour.  Iodine  colours  them  yellow,  and  carmine 
imparts  to  them  a  deep  red  colour.  Sulphuric  acid  renders  them 
green.  These  cylinders  seem  to  be  composed  of  an  altered 
protoplasm  of  the  uriniferous  tube-cells. 

Hyaline  Cylinders. — These  casts  are  homogeneous,  pale, 
transparent,  with  ill-defined  outline,  flexible,  of  varying  length, 
with  defined  or  serrated  extremities,  and  of  a  uniform  diameter 
throughout  their  entire  length  as  a  rule.  Sometimes  they  are 
broken  into  parts,  and  present  the  corkscrew  appearance. 
Dilute  acetic  acid  causes  these  cylinders  to  shrink,  and  they 
dissolve  in  strong  acetic  acid.  Heated  in  the  urine  to  70° 
or  80°  C,  they  dissolve,  or  heated  to  30°  or  40°  C.  in  distilled 
water.    They  are  soon  destroyed  in  alkaline  urine.    The  aspect 


198 


THE  UEINE  IN  HEALTH  AND  DISEASE. 


of  these  casts  is  frequently  altered  by  the  deposition  on  them  of 
diverse  elements  from  the  kidney,  such  as  granulations  of  urates, 

of  phosphates,  crystals  of 
oxalate  of  lime,  fatty 
drops,  round  cells,  blood- 
corpuscles,  etc. 

Cylindroids  (Pseudo- 
Cylinders).— These  ele- 
ments (the  mucous  cylin- 
ders of  Cornil  and  Ean- 
vier)  appear  as  simple 
filaments,  or  as  1  ribbons ' 
of  irregular  outline  and 
unequal  diameter.  Their 
surface  is  striated,  and 
their  extremities  denti- 
lated.  Their  substance  is 
transparent  and  colour- 
less, and  they  are' difficult 
to  distinguish  without  the 
aid  of  staining  agencies. 
Like  other  casts,  their 
substance  may  have  in- 
corporated with  it  other 
elements,  such  as  fat- 
drops,  albuminous  granu- 
lations, blood-corpuscles, 
leucocytes,  epithelial 
cells,  etc.  They  present 
a  wavy  appearance.  Dif- 
ferent salts,  especially  urates,  are  sometimes  deposited  in  the 
uriniferous  tubules,  and  are  thus  eliminated  in  the  form  of 
cylindrical  masses.  These  may  be  readily  distinguished  by 
heating  them  on  a  glass  slide,  with  a  drop  of  hydrochloric  acid, 
when  crystals  of  uric  acid  will  form. 

Spermatic  Cylinders.— These  are  composed  of  casts  from 
the  prostatic  ducts,  and  are  found  in  cases  of  chronic  prostatitis 


Fig.  47.— Hyaline  Cylinders  in  a 
Case  of  Albuminous  Nephritis. 

1,  Desquamated  Renal  Cells  ;  2,  Hya- 
line Cylinder  with  jagged  edges  ;  3, 
Hyaline  Cylinder  with  fragments  of  cells 
adhering,  and  occasioning  a  granular  ap- 
pearance ;  4,  Hyaline  Cylinder  covered 
with  fatty  granulations  ;  5,  Hyaline  Tube, 
of  which  the  smaller  portion  seems  to 
correspond  to  the  intermediate,  or  canal 
of  union. 


PLATE  I. 


4  6 

Fig.  1. — Amyloid  Cast  treated  with  Osmic  Acid. 

Fig.  2. — Colloid  or  Hyaline  Cast  without  any  Reagent. 

Fig.  3.—  Colloid  or  Hyaline  Cast  treated  with  Osmic  Acid. 

Fig.  4. — Mucous  or  Granulo-Fatty  Cylinder. 

Fig.  5. — Fatty  Casts  treated  with  Osmic  Acid. 

Fig.  6. — Granulo-Fatty  Casts. 

[To  face  page  198. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  199 

and  spermatorrhoea.  These  casts  are  hyaline,  and  resemble 
more  or  less  renal  cylinders.* 


Fig.  48. — Spermatozoa  and  Peostatic  or  Spermatic  Casts. 

Epithelial  Cylinders.  —  These  cylinders,  according  to 
Lecorche,  are  formed  of  small  polygonal  cells,  which  can  come 
only  from  the  '  collector  tubes '  of  the  kidney.  They  are  com- 
posed of  the  desquamated  surface  of  the  straight  tubes,  and 
possibly  of  the  descending  limb  of  the  loop  of  Henle.  These 
casts  are  really  very  rare,  and  must  not  be  confounded  with 
mucous  or  granular  casts,  which  present  masses  of  epithelial 
cells.  Their  semeiological  significance  points  to  catarrhal  irrita- 
tion of  the  straight  tubes. 

Haemorrhagic  Casts.  —  These  casts  are  composed  of  red  and 
white  blood  globules,  united  by  fibrine,  and  are  of  medium  dia- 
meter. It  is  rare  to  find  the  red  globules  intact.  Generally  they 
present  an  annular  form,  and  have  lost  their  colouring  matter. 

Pathological  Significance  and  Diagnostic  Value. — The 
presence  of  tube-casts  indicates  inflammation  more  or  less  acute, 
acting  especially  upon  the  secretory  structure  of  the  kidney. 
This  inflammation  may  be  idiopathic,  as  in  cases  of  Bright's 
disease,  or  may  be  due  to  the  action  of  irritants  and  poisons  on 

*  Vide  6  Prostatic  Casts,'  by  D.  Campbell  Black,  M.D.  (Lancet, 
January,  1866),  and  '  Annales  des  Malad.  des  Organes  Genito- 
Urinaires,'  1887,  p.  329. 


200  THE  URINE  IN  HEALTH  AND  DISEASE. 

the  renal  structure,  such  as  cantharides,  strong  diuretics,  bile, 
phosphorus,  etc.,  or  secondarily,  from  the  elimination  of  the 
'  poisonous  debris '  of  such  diseases  as  scarlatina,  during  the 
desquamative  stage,  small-pox,  typhus,  etc.  Urinary  cylinders 
are  never  wanting  in  acute  nephritis  and  amyloid  degeneration 
of  the  kidney.  Casts  are  found  in  the  urine  of  animals  which 
have  been  covered  with  varnish  and  thus  rendered  albuminuric. 
Epithelial  cylinders  indicate  desquamative  nephritis.  If  pus 
corpuscles  be  found  superadded,  the  prognosis  will  be  less  favour- 
able, as  a  greater  intensity  of  inflammation  is  thus  evident. 
Blood-casts  indicate  intense  inflammation,  or  effusion  of  blood 
into  the  parenchyma,  or  calyces  of  the  kidney.  Granulo-fatty 
cylinders  give  evidence  of  fatty  degeneration  of  the  kidne}T, 
especially  if  associated  with  epithelial  cells — Bright's  disease  in 
its  second  stage.  Amyloid  cylinders  point  to  sclerosis  of  the 
kidney.  Hyaline  and  granular  tubes,  especially  if  abundant, 
indicate  chronic  Bright's  disease — the  small  red  granular  kidney. 
They  are  formed  in  tubes  denuded  of  epithelium.  The  urine  is 
often  in  excess  of  the  quantity  secreted  in  health,  and  as  the 
solid  constituents  of  the  urine  are  inadequately  eliminated,  the 
specific  gravity  of  the  urine  is  as  low  as  from  1010  to  1005.* 

In  cases  of  cancer  of  the  kidney  the  epithelial  cells  found  in 
the  urine  are  large,  irregular,  and  present  prolongations,  or 
processes,  with  one  or  more  nuclei. 

According  to  Aufrecht,f  tube-casts  may  be  due  to  an  exudation 
from  the  blood,  or  be  the  product  of  the  renal  epithelium.  He 
cites  the  following  facts  in  favour  of  the  latter  view :  (1)  In 
certain  experiments  he  tried  one  ureter,  when  the  renal 
epithelium  was  seen  to  contain  masses  of  a  hyaline  substance, 
which  subsequently  made  its  way  into  the  lumen  of  the 
tubules  to  form  casts  ;  (2)  albuminuria  may  exist  without  casts ; 
(3)  there  may  be  casts  in  the  urine  without  albuminuria ;  (4) 
casts  may  be  seen  in  the  collecting  tubes  of  a  different  colour, 
and  of  such  a  calibre  that  they  could  not  pass  through  Henle's 
loops.  The  local  origin  of  casts  in  the  tubules  has  been  un- 
doubtedly shown  in  the  cholera  kidney  and  in  that  of  scarlatinal 
nephritis. 

*  Vide  Author's  '  Lectures  on  Bright's  Disease,'  p.  62. 
t  Ceutralh.  f.  inn.  Med.,  May  12th,  1894. 


CHAPTEK  V. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE — 

Continued. 

Inorganic  Substances. 

Compounds  of  ammonia  are  of  frequent  occurrence  in  the  urine, 
and  the  carbonate  of  ammonia  which,  in  the  majority  of  instances, 
communicates  its  alkaline  reaction  to  the  urine,  arises  from  the 
decomposition  of  urea,  either  before  or  after  the  emission  of  the 
urine. 

Carbonate  of  Ammonia  arises  from  the  decomposition  of 
urea  under  the  influence  of  a  special  ferment.  This  decomposi- 
tion takes  place  very  rapidly  in  the  presence  of  pus,  or  mucus, 
and  especially  when  the  temperature  is  elevated.  Hence  it  is  of 
frequent  occurrence  in  cases  of  vesical  catarrh. 

Ammonio-Phosphate  of  Magnesia. — The  formation  of  this 
compound  is  consecutive  to  that  of  the  carbonate  of  ammonia. 
It  forms  in  the  bladder,  and  constitutes  a  form  of  gravel. 

Phosphate  of  Soda  and  Ammonia. — In  normal  urine  there 
exists  a  neutral  phosphate  of  soda  primarily  ;  and  in  consequence 
of  the  presence  of  uric  acid  this  salt  is  transformed  into  acid 
phosphate.  When  ammonia  forms  through  the  decomposition 
of  urea,  the  acid  phosphate  absorbs  it  and'  transforms  it  into  a 
double  phosphate  of  soda  and  ammonia  (NaNH4P04). 

Acid  Urat9  of  Ammonia  (C5H3  (NH4)  N403)  is  found  invari- 
ably in  urine  which  has  become  ammoniacal.  This  urate  is  not 
very  soluble.  On  incineration  it  leaves  no  residue,  and  in  order  to 
distinguish  it  from  uric  acid  the  ammonia  must  be  separated  by 
treating  with  soda.  It  occurs  under  the  form  of  more  or  less 
voluminous  spheres,  which  often  present  longish  spines.  Urates 


202  THE  URINE  IN  HEALTH  AND  DISEASE. 


of  lime  and  magnesia  are  also  found,  but  more  rarely,  in  the 
urine. 

Analysis  of  Ammonia  Salts. — Ammonia  salts  as  existing  in 
the  urine  are  of  two  varieties,  the  one  volatile  at  the  ordinary 
boiling-point,  the  carbonate  of  ammonia  ;  the  other  only  decom- 
posable at  a  more  elevated  temperature,  and  not  evolving  am- 
monia except  through  the  agency  of  fixed  alkalies. 

The  following  is  the  process  of  Schloesing,  modified  by  St. 
Claire  Deville :  Put .  a  known  quantity  of  urine,  50  to  100 
grammes,  for  example,  into  a  small  capsule,  suspended  over  a 
measured  quantity  of  sulphuric  acid,  in  a  crystallizer  whose  base 
is  immersed  in  mercury.  The  jar  is  closed  by  a  plug,  perforated 
by  two  tubes,  the  one  curved,  and  closed  by  a  stop-cock  ;  the 
other  a  pipette,  also  closed  by  a  stop-cock.  The  pipette  is  filled 
with  milk  of  lime  in  graduated  quantity.  The  stop-cock  of  the 
smaller  tube  is  now  opened,  and  a  little  air  is  admitted  into  the 
jar.  The  stop -cock  of  the  pipette  is  now  opened,  and  a  little  of 
the  milk  of  lime  is  permitted  to  fall  into  the  urine.  In  about 
forty- eight  hours  all  the  ammonia  is  evolved,  and  is  absorbed  by 
the  sulphuric  acid.  An  alkalimetric  analysis  will  now  show  the 
quantity  of  ammonia  evolved.  Forty-nine  grammes  of  the 
standard  acid  correspond  to  17  grammes  of  ammonia  ;  it  is  thus 
easy  to  calculate  how  much  ammonia  is  represented  by  10  c.c. 
of  the  standard  acid.  By  means  of  caustic  soda  the  amount  of 
sulphuric  acid  remaining  free  may  be  determined.  The  dif- 
ference represents  the  quantity  of  acid  saturated  by  the  ammonia 
of  the  urine,  and  consequently  its  proportion. 

A  more  rapid  process,  and  one  sufficiently  exact,  consists  in 
the  decomposition  of  the  ammonia  salts  by  the  hypobromite  or 
hypochlorite  of  soda.  For  this  purpose  the  uro-azetometer  of 
Gautrelet-Vieilard  may  be  employed.  Sutton  recommends  the 
following  process :  100  c.c.  urine  are  exactly  neutralized  with 
decinormal  (^y)  soda  or  potash,  as  for  the  estimation  of  free  acid ; 
it  is  then  put  into  a  flask  capable  of  holding  five  or  six  times  the 
quantity,  10  c.c.  of  normal  alkali  added,  and  the  whole  brought 
to  boiling,  taking  care  that  the  bladders  of  froth  which  at  first 
form  do  not  boil  over.  After  a  few  minutes  these  subside,  and 
the  boiling  proceeds  quietly.    When  all  ammoniacal  fumes  are 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  203 


dissipated,  the  lamp  is  removed,  and  the  flask  allowed  to  cool 
slightly ;  the  contents  are  then  emptied  into  a  tall  beaker,  and 
normal  acid  delivered  from  the  burette  with  constant  stirring, 
until  a  fine  glass  rod  or  small  feather  dipped  in  the  mixture,  and 
brought  in  contact  with  violet  litmus-paper,  produces  neither 
a  blue  nor  a  red  spot.  The  number  of  c.c.  of  normal  acid  is 
deducted  from  the  10  c.c.  of  alkali,  and  the  rest  calculated 
as  ammonia;  1  c.c.  of  alkali  =  0-017  gramme  of  ammonia. 
Example :  100  c.c.  of  urine  were  taken,  and  required  7  c.c. 
of  tnq  alkali  to  saturate  its  free  acid;  10  c.c.  of  normal  alkali 
were  then  added,  and  the  mixture  boiled  until  a  piece  of 
moistened  red  litmus-paper  was  not  turned  blue  when  held  in 
the  steam ;  4*5  c.c.  of  normal  acid  were  afterwards  required  to 
saturate  the  free  alkali;  the  quantity  of  ammonia  was,  therefore, 
equal  to  5*5  c.c,  which,  multiplied  by  0*017,  gave  0*0935  gramme 
in  1,000  of  urine. 

Sulphuretted  Hydrogen.— The  urine  may  contain  sulphu- 
retted hydrogen  after  the  inspiration  of  this  gas  or  after  the 
ingestion  of  sulphur.  Its  presence  is  demonstrated  by  acetate 
of  lead. 

Organized  Substances. 

Blood  Corpuscles  (H^moglobine). 
Blood  elements  are  found  in  the  urine  under  two  forms  : 

(a)  As  Hematuria,  in  which  the  urine  contains  blood  cor- 
puscles, which  impart  to  it  an  intensity  of  colour  corresponding 
to  their  quantity. 

(b)  As  Hemoglobinuria,  in  which  the  urine  contains  the 
colouring  principle  of  the  blood,  and  few  or  no  blood  corpuscles. 

Hematuria. — In  this  case  the  urine  is  of  the  colour  of  blood, 
or  of  a  light  brownish  colour.  It  is  opaque,  and  on  standing 
deposits  a  grayish-red  or  grayish-brown  sediment. 

Heller's  Reaction. — To  a  few  c.c.  of  urine  containing  blood, 
add  a  little  caustic  soda,  so  as  to  render  the  liquid  strongly 
alkaline.  Heat  to  boiling.  If  blood  be  present,  a  bottle-green 
colour  results,  and  the  phosphates  are  precipitated  in  fine  flakes 
containing  the  colouring  matter  of  the  blood,  of  a  brownish-red 
colour. 


204 


THE  UBINE  IN  HEALTH  AND  DISEASE. 


Guaiacum  Reaction. — Mix  carefully  1  c.c.  of  tincture  of 
guaiacum    with   an   equal    quantity   of   oxidized  turpentine 

('  Sanitas').  Drop  gently  from 
a  tube  along  the  wall  of  the 
vessel  containing  the  urine.  A 
part  of  the  resin  of  the  guaiacum 
separates  rapidly  under  the  form 
of  a  whitish  precipitate,  which 
becomes  of  a  greenish  colour ; 
but  if  the  urine  contains  the 
smallest  trace  of  blood  there 
forms  below  the  resin  an  indigo- 
blue  coloured  zone,  which  on 
agitation  gives  a  clear  blue 
emulsion.  Or  add  a  few  drops 
of  tincture  of  guaiacum  to  the 
urine,  and  then  an  excess  of 
ozonic  ether — that  is,  a  mixture 
of  peroxide  of  hydrogen  and 
ether.  Shake  the  mixture  :  the 
ether  separates,  and  if  blood  be 
present,  a  fine  sapphire  -  blue 
colour  results.  As  other  substances  besides  haemoglobine  reduce 
the  guaiacum,  this  test  can  be  regarded  only  as  corroborative. 
Hseniin  Reaction.— For  this  reaction  the  coagulum  which  is 

deposited  from  the  urine  is  to 
be  gently  heated  to  dryness 
with  a  fragment  of  chloride 
of  sodium.  Treat  the  mixture 
with  two  or  three  drops  of 
glacial  acetic  acid.  Heat  on 
a  glass  slide.  On  cooling, 
characteristic  crystals  of  hae- 
min  are  found.  These  are 
small  rhomboidal  tablets  of  a 
reddish-brown  colour. 

Lechine's  Reaction.  —Add 
one  drop  of  acetic  acid  to  10  c.c. 


Fig.  49.- 


-Crystals  of  Haemo- 
globine. 


Fig.  50. — Crystals  of  Hkiwin. 


PLATE  II. 


4 

Fig.  1. — Red  Blood- Globules  presenting  different  Degrees 
of  Alteration. 

Fig.  2. — Red  Blood-Globules  presenting  a  rarer  Form  of 
Alteration,  highly  magnified. 
Fig.  3. — Leucocytes — Granular  and  Granulo-Fatty  Changes. 
Fig.  4. — Mucous  Cast  with  altered  White  Globules. 
Fig.  5. — Lining  of  Straight  Tube,  almost  normal. 

[To  face  page  205. 


ABNORMAL  CONSTITUENTS  OF  THE  UEINE. 


205 


of  urine,  and  agitate  with  3  c.c.  of  chloroform.  After  a  few 
minutes'  repose  the  chloroform  becomes  red,  if  the  urine  contain 
the  colouring-matter  of  the  blood.* 


Fig.  51. —Red  Blood  Globules.        'decolorized  in  the  Urine, 

with  Double  Contour. 

Microscopic  Examination  shows  the  blood-globules  under 
the  form  of  small  discoidal  corpuscles  of  a  yellowish  colour, 
slightly  biconcave,  with  well-defined  borders.  In  urine  which 
has  become  alkaline,  however,  and  in  which  the  corpuscles  have 
lain  for  a  considerable  time,  the  globules  become  swollen,  and 
present  serrated  edges.  Sometimes  they  present  a  double 
contour,  and  then  become  discoloured  by  the  solution  of  the 
haemoglobine  in  the  alkali. 

Hemorrhagic  cylinders  are  frequently  met  with  in  the  urine, 
and  possess  an  important  diagnostic  significance  in  relation  to 
renal  haemorrhage.  Rarely  crystals  of  haematoidine  are  found  in 
the  urine. 

Pathological  Significance.  —  To  determine  whether  the 
blood  be  from  the  bladder  or  kidney,  several  points  have  to  be 
considered.  When  at  the  commencement  of  micturition  the 
urine  does  not  contain  blood,  or  only  a  minute  quantity,  and 
the  maximum  of  blood  colour  appears  in  the  last  drops  of 
urine ;  when  the  colour  of  the  urine  is  reddish,  the  reaction 
alkaline  (ammoniacal),  and  the  proportion  of  albumen  is  rela- 

*  Pharm.  Zeitung,  1887. 


206)  THE  UBINE  IN  HEALTH  AND  DISEASE. 

tively  feeble,  there  is  reason  to  suppose  that  the  haemorrhage 
is  of  vesical  origin.  Even  isolated,  each  of  these  symptoms 
would  point  to  this  conclusion. 

Renal  Haemorrhage,  apart  from  traumatic  lesions  and  cancer, 
is  usually  moderate.  The  colour  of  the  urine  is  grayish-brown 
or  reddish-brown.  The  mixture  of  the  blood  with  the  urine  is 
intimate,  the  reaction  is  acid,  and  the  amount  of  albumen 
relatively  abundant.  Elongated  or  vermiform  coagula  of  from 
5  to  10  c.c.  in  length  frequently  form  in  the  ureters.  They  are 
whitish  in  appearance,  sometimes  of  the  size  of  a  quill.  They 
are  most  frequently  found  in  cases  of  renal  haemorrhage. 
Hemorrhagic  cylinders  can  form  only  in  the  kidney. 

Spectrum  Analysis. — Oxyhaemoglobine  presents  two  well- 
marked  absorption  bands  between  the  D  and  E  Frauhenhofer 
lines  (in  the  yellow  and  green).  Methaemoglobine,  a  modifica- 
tion of  haemoglobine  containing  as  much  oxygen  as  oxyhaemo- 
globine, presents  a  characteristic  ray  in  the  red.  According  to 
Hoppe-Seyler,  urine  in  the  fresh  state  never,  or  only  very 


A 

1 
1 

111 

B 

111 

RED 

0RANGJE  YELLOW 

G 

REEN  BLUE  VIOL 

ET! 

C 

i 

Fig.  54.— (a)  Spectrum  of  Haemoglobine  ;  (b)  Spectrum  of  K educed 
Haemoglobine  ;  (c)  Spectrum  of  Urobiline. 

exceptionally,  contains  oxyhaemoglobine,  but  always  methaemo- 
globine. Putrefaction  reduces  methaemoglobine  to  haemoglobine, 
which  by  agitation  with  air  produces  oxyhaemoglobine.  Fresh 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  207 


urines,  then,  give  the  spectrum  of  methsemoglobine  ;  if  long  kept, 
the  spectrum  of  haemoglobine  or  oxyhgemoglobine. 

Hemoglobinuria. — Hemoglobinuria  is  symptomatic  of  exan 
thematous  fevers,  certain  cases  of  poisoning,  and  nervous 
maladies,  etc.  The  colour  of  the  urine  varies  from  ruby  red  to 
black.  In  t}^pical  cases  the  urine  is  clear,  transparent,  and 
approaches  the  colour  of  port-wine.  Notwithstanding  that 
chemical  tests  demonstrate  the  presence  of  the  colouring  matter 
of  the  blood,  microscopic  examination  does  not  reveal  blood 


Fig.  55.— The  Spectroscope. 


corpuscles.  Frequently  hyaline  and  granular  casts  are  found, 
with  a  brownish  detritus.  From  the  chemical  point  of  view  the 
reactions  of  such  urine  are  simply  those  of  a  solution  of  haem  o- 
globine.  Heated  to  boiling,  an  albumen  coagulum  results,  but 
this  albumen  is  not  coagulated  as  ordinary  serum  albumen  in 
flakes  which  settle,  but  immediately  forms  a  brownish  coherent 
coagulum,  which  floats  upon  the  surface,  and  can  be  lifted  there- 
from, and  decolorized  with  boiling  alcohol  and  sulphuric  acid. 

Leucocytes  (Pus). 
Pus  is  found  in  the  urine  in  cases  of  inflammation  of  some 
portion  of  the  genito-urinary  tract.    When  the  amount  is  con- 


208 


THE  UBINE  IN  HEALTH  AND  DISEASE. 


siderable,  and  the  evacuation  is  accomplished  in  a  brief  space  of 
time,  the  existence  of  an  abscess  may  be  inferred,  either  in  the 
kidney  or  in  the  cellular  tissue  of  some  of  the  organs  adjacent  to 
the  pelvis.  In  the  female  the  urine  may  contain  pus  from  the 
vagina  or  uterus.  Urine  containing  pus  is  usually  of  a  pale, 
grayish  yellow,  dirty  colour.  It  presents  a  more  or  less  con- 
siderable grayish  sediment,  which  on  microscopical  examination 

is  found  to  consist  of 

or  7 
/^x  ^-^  pus-cells,  or  leucocytes. 


tents.  These  granulations  conceal  the  nucleus  of  the  pus-cell  (one 
or  two).  The  addition  of  acetic  acid  dissolves  the  granulations, 
and  the  nuclei  become  apparent.  Like  the  blood,  pus  is  formed 
of  two  parts — one  liquid,  or  plasma ;  the  other  solid,  composed 
of  the  opaque  whitish  globules  just  mentioned.  The  plasma  of  pus 
may  be  separated  by  nitration.  It  is  an  amber-coloured,  clear, 
alkaline  liquid,  coagulable  by  heat.  It  contains  the  following 
albuminoid  compounds,  viz.,  globulin c,  serine,  my o sine,  and 
jpyine.  The  last  is  precipitated  by  acetic  acid  as  mucine  is  ;  but 
the  precipitate  is  soluble  in  water,  a  circumstance  which  dis- 
tinguishes it  from  mucine.  Purulent  urine  is  most  frequently 
ammoniacal,  and  its  sediment  forms  a  viscous  filamentous 
mass.  Sometimes  it  is  entirely  transparent,  and  then  all  its 
parts  adhere  so  intimately  that  it  may  be  emptied  from  the  con- 
taining vessel  as  a  coherent  gelatinous  mass.  Sometimes,  under 
the  action  of  carbonate  of  ammonia,  the  cells  undergo  certain 
important  modifications.  They  become  clear,  their  contour  fades, 
and  the  nuclei  are  distinguished  with  difficulty.  In  such  speci- 
mens of  urine  there  are  usually  found  numerous  crystals  of 
ammonio-phosphate  of  magnesia  (triple  phosphate)  and  of  urate 
of  ammonia.    If  a  concentrated  solution  of  potash  be  added  to 


These  cells  are  round, 
often  of  crenated  outline, 
have  the  same  appear- 
ance as  mucus-cells,  are 
about  twice  the  size  of 
the  red  globules  of  the 
blood,  and  are  entirely 
filled  with  granular  con- 


Fig.  56. — Pus  Cells. 
(a)  Normal  ;  (b)  Acted  on  by  Acetic  Acid. 


PLATE  III. 


G  1 

Fig.  1. — Overlapping  Epithelial  Cells  from  the  Vagina. 

Fig.  2. — Vaginal  Epithelial  Cell  with  folded  Edges. 

Fig.  3. — Altered  Vaginal  Cell  (the  Nucleus  deformed). 

Figs.  4  and  5. — Normal  Bladder  Cells  of  the  Rabbit  (Super- 
ficial Layer). 

Fig.  6. — Normal  Cell  from  Rabbit,  Middle  Layer. 

Fig.  7. —Bladder  Epithelial  Cells  as  appearing  in  Urine 
after^Twenty-four  Hours. 

[To  face  page  209. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  209 


urine  containing  pus,  a  gelatinous  coagulum  results ;  while  in 
the  case  of  mucus  it  is  liquefied  and  dissolved  under  like  cir- 
cumstances. In  certain  cases  of  gonorrhoea  pus  filaments  may 
be  found.  Urine  containing  pus  is  necessarily  coagulated  by 
heat,  and  by  filtration  the  pus  globules  and  the  albumen  may 
be  separated.  Sediments  of  earthy  phosphates  which  present 
a  certain  similarity  to  pus  may  be  distinguished  from  it  by  their 
solubility  in  acetic  acid. 

Day's  Test  for  Pus. — The  late  Dr.  Day,  of  Geelong,  recom- 
mended the  following  test  for  pus.  To  the  purulent  urine  add  a 
drop  or  two  of  tincture  of  guaiacum,  when  a  clear  blue  colour  is 
produced.  If  the  pus  be  dry,  before  applying  this  test  it  is 
necessary  to  moisten  it  with  water.  Eecently  oxygenated  water 
has  been  recommended  as  a  test.  It  determines  an  effervescence 
due  to  oxygenation. 

Mucus. 

The  appearance  of  mucus  is  usually  characteristic.  It 
forms  a  flocculent,  cloudy,  semi-transparent  deposit  of  feeble 
coherency.  Owing  to  its  feeble  density,  it  remains  long  sus- 
pended in  the  urine.  It  becomes  fluid  on  the  addition  of 
ammonia,  whereas  pus  becomes  gelatinous.  Urine  containing 
mucus  does  not  necessarily  give  an  albumen  precipitate.  Day's 
test  for  mucus  consists  in  the  application,  first,  of  oxidized 
tincture  of  guaiacum,  which  alone  undergoes  no  change  in  con- 
tact with  mucus,  but  on  the  addition  of  carbolic  acid  or  creosote 
the  colour  of  the  guaiacum  becomes  bright  blue.  On  micro- 
scopic examination  mucus  is  found  to  consist  principally  of 
filaments,  made  more  manifest  by  the  addition  of  acetic  acid, 
and  some  clear,  round  cells.  Whenever  the  addition  of  acetic 
acid  to  urine  causes  a  slight  cloudiness,  the  urine  contains  mucus. 
If  microscopic  examination  reveals  leucocytes,  and  if  albumen 
exist,  there  is  muco-pus  in  the  urine. 

Epithelial  Cells. 
In  the  cloudy  deposit  which  forms  in  normal  urine  most 
frequently  exist  epithelial  cells  from  the  bladder.     The  des- 
quamation of  epithelium  may  take  place  from  the  kidney  to  the 
urethra,  and  the  origin  of  the  cells  is  determined  by  their  special 

14 


210 


THE  UKINE   IN  HEALTH  AND  DISEASE. 


character.  The  epithelial  covering  of  the  genito-urinary  tract 
comprises  three  layers :  the  superior  layer,  formed  of  large 
rounded  or  polygonal  scales,  with  a  nucleus ;  the  middle  layer, 
composed  of  spindle  cells,  whose  tapered  extremity  is  insinuated 
into  the  inferior  layer ;  and  the  innermost  layer,  composed,  of 
ovoid  elongated  cells,  smaller  than  those  of  the  surface.  Des- 
quamation of  the  superficial  cells  is  constantly  taking  place. 
The  epithelial  cells  most  frequently  found  are  those  of  the 
bladder.  They  appear  as  transparent  rectangular  plaques,  with 
rounded  or  elliptic  angles,  with  a  nucleus  with  a  border  more 
defined  than  that  of  the  cells  of  the  vagina.  They  are  isolated, 
or  aggregated  together  in  plaques,  of  greater  or  less  size.  By 
their  borders  they  are  in  apposition  to  one  another,  and  some- 
times they  are  slightly  imbricated.  These  cells  are  found  in  the 
urine  of  females  as  well  as  of  men.  In  the  former  case  vaginal 
epithelium  may  be  found.  These  are  abundant  when  the 
vagina  is  the  seat  of  inflammation.  They  are  of  the  same  form 
as  the  cells  of  the  bladder,  but  are  larger,  with  thinner  edges 
and  a  smaller  central  nucleus.  These  cells  resemble  those  of 
the  inferior  portion  of  the  ureter  and  prepuce. 

The  cells  of  the  neck  of  the  bladder  are  caudate.  They  pro- 
bably represent  the  middle  layer  of  the  epithelial  covering.  The 
cells  of  the  ureters  and  pelvis  of  the  kidney  are  smaller  than  the 
preceding,  and  are  club-form,  having  a  nucleus  in  the  head,  or 
enlarged  portion. 

The  epithelium  of  the  ureter  is  stratified  pavement.  The  cells 
are  long  and  cylindrical.  They  are  granular,  and  above  the 
oval  nucleus  there  is  found  one,  rarely  two,  brilliant  drops,  which 
resist  the  action  of  acetic  acid. 

The  cells  which  come  from  the  pelvis  of  the  kidney  are  fre- 
quently small,  round,  or  oval,  with  large  nuclei,  and  are  generally 
united  in  plaques.  This  grouping  is  very  significant,  for  if  along 
with  it  there  is  acidity  of  the  urine,  we  have  here  a  pathog- 
nomonic distinction  between  pyelitis  and  cystitis.  Kenal 
epithelium  is  formed  of  round  or  polyhedral  cells,  generally 
isolated,  and  with  a  granular  or  clear  protoplasm,  granular  in 
the  cells  of  the  tubuli  contorti,  clear  in  those  of  the  descending 
branch  of  the  loop  of  Henle.    The  nucleus  is  large  and  distinct. 


PLATE  IV. 


Fig.  1. — Cells  from  the  Straight  Tubes. 

Fig.  2. — Fatty  Debris,  without  Nucleus,  from  the  Convoluted 
Tubes. 

Fig.  3. — Irregular  Fatty  Mass  from  the  same  region. 
Fig.  4.— Overlapping  Epithelial  Cells  from  the  Vagina. 
Fig.  5. — Normal  Cells  from  Middle  Layer  of  the  Bladder. 
Fig.  6.— Nucleated  Fatty  Mass  from  the  Convoluted  Tubes. 
Fig.  7. — Normal  Cells  from  the  Deep  Layer  of  the  Bladder 
and  Ureter. 

[To  face  page  210. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  211 


These  cells  undergo  great  modifications  as  the  result  of  patho- 
logical processes.  Thus,  in  cases  of  fatty  degeneration  of  the 
kidney  they  contain  small  refractive  fatty  granulations,  and 
their  volume  is  much  augmented.  They  are  easily  recognised. 
When  they  are  found  on  tube-casts,  or  when  united  with  other 
elements,  they  constitute  epithelial  casts. 

The  epithelial  cells  of  the  urethra  are  elongated,  cylindrical,  and 
slender  inferiorly.  They  are  granular,  and  possess  an  oval  nucleus. 

The  presence  of  epithelial  cells  in  the  urine  is  of  no  patho- 
logical importance  when  in  small  quantity.  If  abundant,  they 
indicate  a  corresponding  amount  of  desquamation,  and  conse- 
quently inflammation  of  some  portion  of  the  genito-urinary  tract. 
The  form  of  the  cell  may  indicate  the  seat  of  the  disease. 
Abundant  desquamation  is  almost  invariably  associated  with  the 
formation  of  pus,  and  leucocytes  and  albumen  are  then  found 
in  the  urine.  This  applies  more  especially  to  cystitis,  for  in 
nephritis  tube-casts  take  the  place  of  epithelial  cells. 

Spermatozoa. 

Spermatozoa  are  found  in  the  urine  after  coitus,  after  involun- 
tary seminal  emission  ;  usually  in  cases  of  spermatorrhoea  ;  after 
epileptic  attacks ;  may  be  passed  from  the  urethra  at  stool, 
especially  when  the  bowels  are  constipated,  and  when  the 
prostatic  ducts  are  relaxed  and  atonic  ; 
in  cases  of  chronic  prostatitis,  and 
during  the  course  of  several  constitu- 
tional diseases,  such  as  typhoid  fever,  and 
after  apoplectic  and  epileptic  attacks.* 
Like  pus,  the  semen  is  composed  of  a 
fluid  and  a  solid  portion.  Urine  con- 
taining semen  is  not  usually  markedly 
cloudy.  The  liquid  portion  contains  an 
albuminous  principle,  sjpermatine,  which  Fig.  57. — {a)  [b)  Spek- 
is  precipitated  by  acetic  acid,  and  matozoa  laegely  Mag- 
soluble  in  an  excess,  by  which  it  is 

differentiated  from  mucine.    Allowed  to  stand,  however,  for 

*  Vide  '  Prostatorrhoea/  by  Author  (Lancet,  October,  1882),  and 
'  The  Functional  Diseases  of  the  Urinary  and  Reproductive  Organs,' 
second  edition  (Churchills,  London). 


212  THE  URINE  IN  HEALTH  AND  DISEASE. 


some  time  in  a  conical  glass,  the  semen  deposits  in  from  six 
to  eight  hours,  when  it  may  be  examined  microscopically,  and 
the  characteristic  appearance  of  the  spermatozoa  be  demon- 
strated. Spermatozoa  resemble  the  tadpole  in  form,  com- 
posed as  they  are  of  a  head,  which  is  ovoid  or  triangular, 
and  a  long  filiform  tail.  In  semen  recently  ejaculated  the 
spermatozoa  exhibit  great  activity.     Sometimes  spermatozoa 


Fig.  58.— Spermatozoa,  with  Fig.  59. — Spermatozoa,  Blad- 

Acid  Urate  of  Ammonia,  Blad-  der  Epithelium,  and  Prostatic 

der  Epithelium,  and  fragments  Casts  (passed  from  Urethra  at 

of  Prostatic  Casts  (passed  at  stool), 
stool). 


are  found  in  fragments  in  the  urine,  the  tail  especially  being 
broken ;  notwithstanding  this,  the  head  can  be  easily  recognised. 
In  the  case  of  copious  seminal  losses,  besides  the  spermatozoa, 
certain  particles  like  sago  grains  (corpuscles  of  Lallemand- 
Trousseau)  are  found  in  the  urine.  According  to  Furbringer, 
they  are  composed  of  a  substance  analogous  to  globuline,  and 
come  from  the  seminal  vesicles.  In  the  absence  of  spermatozoa 
these  bodies  do  not  possess  any  diagnostic  significance.  If 
semen  be  allowed  to  dry  on  a  glass  slide,  prismatic  or  pyramidal 
colourless  or  yellow  crystals,  grouped  in  a  stellar  form,  are 
observed  (crystals  of  Bottcher).    According  to  Schreiner,  these 


PLATE  V. 


Fig.  1. — Gonococcus  enlarged  about  200  Diameters. 

Fig.  2. — Gonococci  in  Pus  Cells,  (d)  Pus  cell,  (p)  Cell  proto- 
plasm contracted  by  alcohol,    (y)  Gonococci  (12  immer.  objective). 

Fig.  3. — Isolated  Gonococci  in  Epithelial  Cells,  {a)  Cell 
containing  at  each  extremity  a  mass  of  gonococci.  {b)  A  mass  of 
gonococci  upon  an  epithelial  cell,  (c)  Cell  with  a  few  gonococci.  {d) 
Gonococci  outside  the  cell. 

[To  face  page  213. 


ABNORMAL  CONSTITUENTS  OF  THE  URINE.  213 


crystals  are  a  combination  of  phosphoric  acid  with  an  organic 
substance. 

Spermatic  sediments  frequently  contain  crystals  of  oxalate  of 
lime,  especially  in  cases  of  spermatorrhoea,  leucocytes,  epithelial 
cells,  granules  of  urates,  crystals  of  uric  acid  and  of  triple 
phosphate. 

Organisms  found  in  Urine. 

The  parasitic  animal  most  frequently  found  in  the  urine,  in 
Europe,  is  Echinococcus  hominis.  It  is  either  found  in  sus- 
pension in  the  urine  or  in  its  sediments.  It  is  easily  distin- 
guished by  its  hooklets  and  stratified  membranous  scales. 

In  hot  countries,  and  notably  in  Egypt  and  South  Africa,  the 
urine  is  often  found  to  contain  the  egg  and  ciliated  embryos  of 
the  Distoma  hcematobium  or  Bilharzia  hcematobia.  This  worm 
is  also  found  in  the  vena  per  tee  and  its  branches,  as  well  as  in  the 
venous  plexus  of  the  bladder.  The  eggs  are  deposited  in  great 
number  by  the  female  in  the  interior  of  the  vessels,  and  within 
the  vesical  mucous  membrane,  and  ultimately  perforate  the 
membrane,  hematuria  being  the  result.  In  this  case  the  urine  is 
bloody,  and  deposits  a  reddish  flocculent  sediment,  containing 
blood-crystals,  leucocytes,  and  eggs  of  the  Distoma.  In  the  East 
Indies  there  is  found  in  the  urine  and  in  the  b^ood  of  persons 
suffering  from  chyluria,  embryos  of  the  Filaria  sanguinis 
hominis,  which  have  also  been  observed  by  Bresil  in  endemic 
hematuria,  this  affection  being  due  to  their  existence  in  the 
blood.  Almost  invariably  chyluria  is  accompanied  by  haematuria 
(hsemato-chyluria).  The  so-called  bacillus  of  tuberculosis  is 
stated  to  be  found  in  the  urine  of  persons  suffering  from  phthisis. 
It  is  thus  held  to  constitute  a  valuable  differentiating  feature 
between  typhoid  fever  and  miliary  tuberculosis  of  the  genito- 
urinary system.  Sometimes  there  is  accidentally  found  in  the 
urine  Trichomonas  vaginalis,  a  parasite  living  in  the  vaginal 
mucus  ;  the  Bodo  or  Cercomonas  urinarius  described  by  Hassal 
in  alkaline  urine ;  the  Oxyuris  vermicularis ,  whose  habitat  is 
the  inferior  portion  of  the  intestine ;  the  Strongylus  gig  as 
from  the  kidney ;  the  Ascaridis  lumbricoides  and  its  eggs, 
passing  through  an  abnormal  communication  from  the  intestine 


214  THE  UKINE  IN  HEALTH  AND  DISEASE. 

to  the  bladder.  Of  Saccharomycetes,  the  Saccharomyces  urince, 
which  is  probably  identical  with  the  yeast  fungus,  Saccharo- 
myces cerevisice,  has  been  found  in  diabetic  urine.  These  cells 
are  ovoid,  and  brilliant,  and  of  about  the  size  of  a  red  blood- 
corpuscle.  Sarcinoz  may  also  be  found  in  the  urine,  indepen- 
dently of  their  existence  in  the  stomach. 

According  to  Pasteur,  Tieghem,  and  Miguel,  the  Micrococcus 
and  Bacillus  urinai,  which  are  the  cause  of  the  decomposition  of 
urea,  may  also  be  found  in  the  urine. 

In  acute  infectious  maladies,  such  as  diphtheria,  typhoid  fever, 
scarlet-fever,  small-pox,  etc.,  a  large  quantity  of  bacteria  are 
often  found  in  the  urine,  almost  invariably  with  the  presence  of 
albumen.  In  cases  of  gonorrhoea  the  Gonococcus  of  Ncisser 
often  exists  in  the  urine.  This  element  is  by  no  means  pathog- 
nomonic of  gonorrhoea,  as  many  cases  of  gonorrhoea  have  been 
observed  where  it  was  absent.  This  microphyte  is  found  in  the 
purulent  deposit  in  the  form  of  small  round  or  oval  grains,  most 
frequently  aggregated  in  groups.  They  are  readily  stained 
with  methylene  blue  and  fuchsine. 


PLATE  VI. 


Fig.  1. — Bilharzia  H^ematobia.  The  inferior  extremity  of  the 
female  protrudes  from  the  gynsecophoric  canal  of  the  male.  (6,  c,  d) 
Male,    (a)  Mouth-sucker.    (e,f)  Female  in  part  free. 

Fig.  2. — Two  Eggs  of  Bilharzia  ILematobia.  (a)  With  large 
segmentation  of  the  vitellus.    (b)  With  vitelline  granulations. 

Fig.  3.— (a,  b,  c)  Embryos  of  rilaria.  {a)  Head.  (6)  Tail,  (e)  Body 
(d)  Egg  containing  an  embryo,  (e)  Egg  showing  vitelline  segmen- 
tation. 

[  To  face  page  214. 


PLATE  VII. 


Fiji  Kf  2 


Fig.  1. — Sarcin^  Urin^e.  (a)  Group  of  sixteen,  (b)  Group  of  four. 
Fig.  2. — Micrococcus  Ure,e. 

Fig.  3. — Ferment  of  Saccharine  Urine,  (a)  Cells  in  opposi- 
sition  to  each  other. 

Fig.  4. — Penicillium.    (s)  Spore  in  mycellium  tube. 
Fig.  5. — Mass  of  Micrococci  in  Albuminous  Urine. 
Fig.  6. — Yeast  Cells. 
Fig.  7. — Vibrios. 

Fig.  8. — Bacilli,  (a)  Isolated  bacillus.  (b)  Bacilli  joined  to- 
gether,   (c)  Chain  of  bacilli. 

Fig.  9. — Yeast  Cells,  {a)  Oval  cells.  (6)  Cells  joined  together, 
(c)  Bacteria. 

[To  follow  Plate  VI. 


CHAPTEK  VI. 


SEDIMENTS. 

Under  ordinary  conditions  the  normal  and  pathological  elements 
which  have  engaged  attention  in  the  foregoing  pages  are  found 
in  a  state  of  solution  in  the  urine.  When,  however,  there 
happens  to  be  either  relatively  or  absolutely  an  augmentation 
of  those  constituents  in  the  urine,  they  may,  in  consequence, 
undergo  precipitation,  either  in  the  urinary  passages  or  in  the 
urine  after  it  is  voided  from  the  bladder  and  has  become  cold. 
In  the  former  case  the  urine  is  more  or  less  milky  when  passed, 
while  in  the  latter  it  is  limpid  and  transparent.  In  other  cases 
the  urinary  sediment  is  due  to  hyperacidity  of  the  urine,  or,  on 
the  contrary,  to  an  absence  of  the  normal  acidity.  There  are 
certain  urinary  constituents  which  continue  in  solution  in 
normally  acid  urine,  but  which  undergo  precipitation  when  the 
urine  becomes  either  preternaturally  acid  or  unduly  alkaline, 
and  this  change  may  take  place  either  before  or  after  the 
emission  of  the  urine.  Sometimes  new  insoluble  combinations 
are  formed.  Sediments  may  thus  be  composed  of  bodies  which 
on  account  of  their  insolubility  are  only  found  in  suspension  in 
the  urine,  these  constituents  being  always  of  an  organized 
pathological  nature,  and  designated  organized  sediments,  in 
contradistinction  to  the  non-organized  sediments,  which  may 
be  composed  either  of  mineral  or  organic  substances. 

Sediments  may  thus  be  frequently  a  combination  of  non- 
organized mineral  bodies  or  of  organized  organic  elements. 
When  the  sediments  form  in  the  urinary  passages,  and  are 
detained  there,  they  may  become  concretions  of  more  or  less 


216  THE   URINE   IN  HEALTH  AND  DISEASE. 


size.  In  small  form  they  may  be  expelled  with  the  urine  as 
gravel ;  in  larger  size  they  may  become  renal  or  vesical  calculi. 

Examination  of  Sediments.  —  In  order  to  determine  the 
nature  of  urinary  sediments,  both  microscopic  and  chemical 
examination  are  most  frequently  required.  As  a  preliminary 
step,  however,  the  sediment  must  be  isolated.  In  order  to 
accomplish  this,  the  urine  is  decanted  into  a  conical  glass,  and 
allowed  to  stand  undisturbed  until  a  deposit  takes  place.  The 
clear,  supernatant  fluid  is  then  poured  off  carefully,  and  a 
pipette  introduced  into  the  remaining  portion.  Holding  the 
pipette  in  a  vertical  position,  the  deposit  accumulates  in  its 
narrower  portion,  and  it  can  now  be  transferred  to  an  object- 
glass.  Microscopic  examination  can  then  be  made  with  a  power 
varying  from  200  to  400  diameters.  A  chemical  examination 
may  be  made  by  allowing  a  drop  or  two  of  the  reagent  to 
penetrate  between  the  slide  and  the  cover-glass. 

Non-Organized  Sediments.  — The  non-organized  sediments 
most  frequently  met  with  are  uric  acid  and  urates,  oxalate  of  lime 
and  earthy  phosphates  (phosphate  of  lime  and  triple  phosphate) ; 
and  more  rarely  xanthine,  hippuric  acid,  tyrosine,  bilirubine, 
indigotine,  haematoidine,  and  carbonate  and  sulphate  of  lime. 

Distinctive  Characters.  —  The  following  table  exhibits  the 
differentiating  features  of  the  sediments  of  this  group  : 

I.  The  Urine  has  an  Acid  Keaction. 

A.  The  Sediment  is  Amorphous, 

1.  It  is  composed  of  small  granules  which  dissolve  on  heating ; 
acetic  acid  dissolves  them,  and  after  some  hours  small  rhomboidal 
tables  of  uric  acid  separate  (crystals  of  uric  acid  and  of  oxalate 
of  lime  may  also  be  contained  in  the  sediment). 

The  sediment  is  composed  of  urates  (vide  pp.  74  and  75). 

2.  The  sediment  presents  the  appearance  of  dumb-bell  crystals  , 
and  is  insoluble  in  concentrated  acetic  acid,  but  soluble  in  hydro- 
chloric acid  without  separation  of  crystals. 

The  sediment  consists  of  oxalate  of  lime  (vide  pp.  93  and  94). 

3.  The  sediment  is  insoluble  in  acetic  acid  and  concentrated 
hydrochloric  acid. 

It  consists  of  sulphate  of  lime. 


SEDIMENTS. 


217 


4.  The  sediment  consists  of  round,  refractive  bodies  of  a 
pearly  colour. 

It  consists  of  fat  (vide  p.  195). 

5.  The  sediment  consists  of  yellow  granular  masses. 
It  consists  of  bilirubine  (vide  p.  224). 

B.  The  Sediment  is  Crystalline. 

1.  Yellow  or  brown  crystals  of  rhomboidal  form,  isolated  or 
grouped  in  diverse  manners,  alone  or  accompanied  with  urates 
and  oxalate  of  lime,  soluble  in  soda  ;  and  the  addition  of  concen- 
trated hydrochloric  acid  gives  after  the  lapse  of  a  few  hours 
small  yellow  rhomboidal  plates. 

Uric  acid,  (vide  p.  70). 

2.  Colourless  octahedral  crystals,  yellow  in  the '  case  of  urine 
containing  bile,  transparent,  very  refractive,  envelope  form, 
sometimes  of  quadrangular  prismatic  forms,  terminated  by 
pyramids,  insoluble  in  acetic  acid,  but  soluble  in  hydrochloric 
acid. 

Oxalate  of  lime  (vide  p.  93). 

3.  Large  crystals  of  the  coffin-lid  shape,  in  urine  faintly  acid, 
in  appearance  somewhat  similar  to  oxalate  of  lime  crystals,  but 
soluble  in  acetic  acid. 

Triple  phosphates  (vide  pp.  222,  223). 

4.  Small  tubular  crystals,  regular  and  six  sided,  insolmVe  in 
acetic  acid,  but  soluble  in  ammonia. 

Cystine  (vide  pp.  108  and  109). 

5.  Colourless  needle-shaped  crystals,  insoluble  in  acetic  acid 
and  soluble  in  ammonia.  The  addition  of  hydrochloric  acid 
causes  the  deposition  of  small  hexagonal  plates. 

Xanthine  (vide  p.  224). 

6.  Large  rhombic  crystals,  strongly  refractive,  elongated, 
and  very  fine.  Their  angles  are  rendered  opaque  and  de- 
stroyed by  carbonate  of  ammonia  ;  frequently  found  in  alkaline 
urine. 

Basic  phosphate  of  magnesia  (vide  p.  114). 

7.  Isolated  or  grouped  prisms,    (a)  Soluble  in  ammonia. 
Hippuric  acid  (vide  p.  83). 

(b)  Insoluble  in  ammonia  and  acids. 
Sulphate  of  lime. 


218 


THE  URINE  IN  HEALTH  AND  DISEASE. 


8.  Cuneiform  prisms  terminating  in  points,  isolated  or  grouped 
together  in  stellar  form ;  soluble  in  acetic  acid  and  segregating 
in  ammonia. 

Neutral  phosphate  of  lime. 

9.  Tufts  of  fine  needle-like  crystals,  insoluble  in  acetic  acid, 
and  soluble  in  ammonia  and  hydrochloric  acid. 

Tyrosine  {vide  p.  224). 

10.  Small  rhomboidal  tables  of  a  yellow  colour,  and  accom- 
panied by  amorphous  granular  masses  of  a  similar  colour, 
soluble  in  soda ;  and  on  contact  with  acetic  acid  they  surround 
themselves  with  a  multicoloured  areola,  in  which  a  green  zone  is 
observed. 

Bilirubine  (vide  p.  224). 

11.  Needle-formed  crystals,  sometimes  rhombic,  and  yellow  or 
brownish-yellow,  becoming  blue  in  contact  with  nitric  acid. 

Hcematoidine. 

II.  The  Urine  has  an  Alkaline  Reaction. 

If  the  urine  becomes  alkaline  only  after  emission,  it  may  con- 
tain such  sediments  as  uric  acid,  oxalate  of  lime,  sulphate  of 
lime,  etc.  If  the  urine,  on  the  other  hand,  is  eliminated  with 
an  alkaline  reaction,  or  if  it  deposits  a  sediment  while  it  is 
becoming  alkaline,  the  following  sediments  may  be  found  : 

A.  The  Sediment  is  Amorphous. 

1.  It  is  composed  of  small  granules  soluble  in  acetic  acid : 
(a)  Without  evolving  gases — Earthy  phosphates. 

b)  Evolving  bubbles  of  gas  —  Carbonate  of  lime. 

2.  Masses  in  form  of  dumb-bells,  soluble  in  acetic  acid,  with 
disengagement  of  gas  bubbles. 

Carbonate  of  lime. 

3.  Spheroidal  masses  of  a  dark  colour,  with  crystalline  points, 
soluble  in  hydrochloric  and  acetic  acids,  with  subsequent  deposition 
of  rhomboidal  tables  of  uric  acid. 

Urate  of  ammonia  (vide  p.  75). 

B.  The  Sediment  is  Crystalline. 

1.  Large  colourless  prisms  of  coffin-lid  shape,  very  soluble 
in  acetic  acid. 

Ammonio- phosphate  of  magnesia  (vide  p.  109). 


SEDIMENTS. 


219 


2.  Masses  of  blue  needle-formed  crystals,  and  small  tabular 
blue  crystals. 

Uroglaucine  or  indigotine. 

Uric  Acid  and  Urates. — Sediments  of  urates  are  most  fre- 
quently observed  in  acute  febrile  affections,  such  as  in  acute 
rheumatism,  pneumonia,  etc.,  or  during  exacerbations  of  chronic 
affections,  especially  in  disorders  of  the  digestive  apparatus, 
such  as  dyspepsia  and  chronic  gastric  catarrh ;  and  in  affections 
of  the  respiratory  passages,  such  as  dyspnoea,  asthma,  pulmonary 
emphysema,  etc.  The  formation  of  urates  in  the  urine  is  not 
always  necessarily  due  to  the  excess  of  uric  acid  in  the  urine. 
In  cases  of  rheumatism,  for  example,  urates  are  found  in  abund- 
ance in  the  urine,  while  the  amount  of  uric  acid  is  usually 
normal.  It  is  to  the  presence  of  acid  phosphates  in  the  urine 
that  the  precipitation  of  urates  is  most  frequently  to  be  ascribed, 
the  neutral  urates  being  thus  transformed  into  acid  salts,  which 
are  much  less  soluble  ;  or  otherwise,  the  volume  of  urine  elimi- 
nated being  diminished,  there  is  not  a  sufficiency  of  water  to 
hold  the  urates  in  solution.  Cooling  of  the  urine  also  causes  a 
precipitation  of  the  urates,  as  they  are  much  more  soluble  in  hot 
than  in  cold  solutions.  Hence  deposits  of  urates  may  be  found 
in  the  urine  of  perfectly  healthy  individuals,  especially  after 
violent  physical  exertion,  large  ingestion  of  food,  after  abundant 
sweatings,  and  during  winter,  the  urine  being  exposed  to  a  low 
temperature.  .  Cylindrical  masses  composed  of  urates  are  not 
infrequently  observed  in  the  urine  of  infants,  these  being  of  a 
brown  or  reddish  colour,  and  originating  in  the  renal  tubes.  The 
decomposition  of  neutral  urates  by  acid  phosphates,  during  the 
earlier  stages  of  the  decomposition  of  urine,  causes  a  deposition 
of  acid  urates  and  uric  acid  {vide  p.  220). 

Sediments  of  free  uric  acid  are  of  rarer  occurrence.  They 
are  sometimes  found  alone,  at  other  times  accompanied  by 
urates.  In  the  former  instance  they  are  expelled  with  the  urine 
in  the  form  of  uric  acid  gravel,  in  which  case  they  originate  in 
the  urinary  passages. 

Characters  of  Urates. — Deposits  of  urates,  as  we  have  already 
seen,  are  of  yellow  or  brick-red  colour,  according  as  urinary  or 
hepatic  pigments  predominate.    They  usually  consist  of  a  mixture 


220  THE  URINE  IN  HEALTH  AND  DISEASE. 


of  various  urates,  most  frequently  of  potassium  and  sodium, 
sometimes  urate  of  ammonia,  and  more  rarely  of  urate  of  lime 


Fig.  60. — Uric  Acid.  Fig.  61.— Uric  Acid. 


and  magnesia.  Deposits  of  urates  are  not  infrequently  combined 
with  free  uric  acid  and  oxalate  of  lime. 

Examined  microscopically,  these  deposits  present  the  appear- 
ance of  fine  amorphous  granulations  irregularly  grouped,  and  of 


Fig.  62.— Urate  of  Sodium.  Fig.  63.— Urate  of  Ammonia. 
easy  solubility  by  heating,  precipitating  again  when  cooling  takes 
place.    Should  the  proportion  of  urates  be  so  considerable  as  to 


SEDIMENTS. 


221 


render  obscure  the  presence  of  other  sediments,  such  as  uric 
acid  and  oxalate  of  lime,  separation  may  be  effected  by  filtering 
the  heated  urine  :  the  urates  will  pass  through,  and  the  uric  acid 
and  the  oxalate  of  lime 
will  remain  on  the  filter. 
Treated  with  hydrochloric 
acid,  deposit    of  urates 
yields  uric  acid. 

Urate  of  Ammonia.— 
This  urate  is  most  fre- 
quently found  in  alkaline 
urine,  in  combination  with 
earthy  phosphates,  and 
in  the  form  of  fine  granu- 
lations. 

Uric  Acid  Sediments 
present  the  form  and 
characteristics  already  de- 
scribed (vide  p.  70). 

Hippuric  Acid. — Sedi- 
ments of  hippuric  acid  are  rare  (vide,  p.  83  et  seq.).  Hippuric 
acid  crystals  resemble  in  appearance  certain  forms  of  uric  acid 
and  of  triple -phosphate. 
They  are  distinguished 
from  the  former  by  not 
giving  the  murexide  re- 
action, and  from  the 
latter  by  their  insolubility 
in  hydrochloric  acid. 

Oxalate  of  Lime.  — 
Occasionally,  in  perfect 
health,  oxalate  of  lime 
may  be  found  in  the  urine. 
It  may  exist  as  a  sediment, 
or  be  suspended  in  the 
mucus  of  the  urine.  It  exists  in  considerable  abundance  in 
the  urine  in  certain  diseases,  in  connection  with  the  oxalic 
acid  diathesis,  and  after  the  ingestion  of  certain  vegetables. 


Fig.  64. — Hippuric  Acid. 
(a)  Rhombic  prisms  ;  (b)  needle  form. 


Oxalate  of  Lime. 


222  THE  URINE  IN  HEALTH  AND  DISEASE. 


Oxalate  of  lime  precipitates  from  the  urine  simultaneously  with 
acid  urates  and  uric  acid. 

Sometimes  the  crys- 
tals of  oxalate  of  lime 
resemble  certain  forms 
of  chloride  of  sodium 
and  triple  phosphate. 
From  the  former  they 
are  distinguished  by 
their  insolubility  in 
water,  and  from  the 
latter  by  their  insolu- 
bilit}7  in  acetic  acid. 

Earthy  Phosphates. 
—  Sediments  of  earthy 
phosphates  are  usually 
Fig.  66.  —  Triple  Phosphates   (Phos-  found  in  chronic  dis- 
phates  of  Ammonia  and  Magnesia).      eases,  such  as  phthisis, 
rickets,  mollities  ossium,  etc.    These  phosphates  are  deposited 
from  the  urine  in  consequence  of  its  becoming  neutral  or 
alkaline,  and  being  thus  incapable  of  holding  the  earthy  phos- 
phates in  solution.  If 


the  urine  contain  a  sedi- 
ment of  earthy  phos- 
phates when  voided,  it 
is  evident  that  the  sedi- 
ment forms  within  the 
bladder,  and  is  probabty 
associated  with  some 
inflammatory  condition 
of  the  genito-  urinary 
tract.  Long  persistence 
of  earthy  phosphates  in 
the  urine  would  pro- 
bably indicate  vesical 

Fig.  67.— Triple  Phosphates  calculi. 

(Feathery  Form ).  Characters  of 

Earthy  Phosphates.— The  triple-phosphate  presents  the  above 
appearance  (Fig.  66).    The  crystals  are  of  considerable  size,  and 


SEDIMENTS. 


223 


are  very  soluble  in  acetic  acid.  When  the  deposition  of  earthy 
phosphates  is  the  result  of  rapid  evaporation,  the  crystals  present 
the  "  feathery"  form  (Fig.  67). 

Phosphates  of  lime  and  magnesia  deposit  from  urine  which 
has  become  alkaline, 
or  is  voided  as  such. 
They  present  the  form 
of  amorphous,  trans- 
parent, and  rounded 
plaques,  distinguishable 
from  urates  in  not  being 
dissolved  by  heating. 
These  phosphates  may 
exist  alone,  or  be  com- 
bined with  ammonio- 
phosphate  of  magnesia. 
The  deposit  may  be  so 
thick  as  to  be  mistaken 
for  pus. 
Phosphate  of  Lime 


Stellar  Phosphates  of  Lime. 


Fig.  68. 

is  found  in  the  urine  in  the  form  of  prismatic  crystals,  colour- 
less, and  isolated  or  in  tufts.  It  is  distinguished  from  uric  acid 
by  its  solubility  in  acetic  acid. 

Phosphate  of  magnesia  is  sometimes  found  in  neutral  or  con- 
centrated alkaline  urines  in  the  form  of  fine  refractive  rhom- 
boids. When  the  urine  is  not  coloured  by  pigments  to  an  ab- 
normal extent,  the  deposits  of  earthy  phosphates  present  a  white 
appearance.  They  are  insoluble  in  water  and  in  alkalies,  but 
dissolve  readily  in  mineral  acids  and  acetic  acid. 

Carbonate  of  Lime.  —  Sometimes  crystals  of  carbonate  of 
lime  are  found  mixed  with  the  earthy  phosphate  deposits  of  the 
dumb-bell  variety.  They  are  distinguished  from  oxalate  of  lime 
crystals  of  like  form  by  their  easy  solubility  in  acetic  acid. 

Sulphate  of  Lime. — In  rare  instances  this  salt  is  found  in 
the  urine  under  the  form  of  colourless  elongated  needles  or 
tubular  crystals,  insoluble  in  ammonia  and  acetic  acid,  and 
sparingly  soluble  in  nitric  and  hydrochloric  acids. 

Cystine  {vide  p.  179). — Deposits  of  cystine  are  rare  in  the 


224 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


urine.  They  may,  however,  persist  a  long  time  in  the  urine 
without  any  evident  constitutional  derangement. 

Xanthine. — The  presence  of  xanthine  in  the  urine  was  first 

demonstrated  by  Bence  Jones 
in  a  case  of  nephralgia.  Xanthine 
crystals  are  of  two  forms  (Fig.  a, 
and  the  form  b).  The  latter 
are  produced  when  the  xanthine 
is  dissolved  by  heating  (thus 
contra-distinguished  from  uric 
acid),  treated  with  hydrochloric 
acid,  and  evaporated.  These 
crystals  are  then  deposited.  They 
are  soluble  in  water. 

Tyrosine. — In  cases  of  yellow 
atrophy  of  the  liver  tyro- 
sine has  been  found  as  a  urin- 
ary sediment. 

Bilirubine.  —  In  certain 
cases  of  jaundice  and  pyelitis, 
bilirubine  has  been  found 
as  a  urinary  deposit.  It 
either  presents  in  an  amor- 
phous form  or  its  character- 


Fig.  70.— Tyrosine.  Fig.  71.— Bilirubine. 

istic  crystalline  form.  It  is  of  a  yellow  or  brown  colour,  and  is 
very  soluble  in  alkalies  and  chloroform.  With  nitric  acid  it 
gives  the  special  bile-pigments'  reaction. 


SEDIMENTS. 


225 


Uroglaucine,  or  Indigotine.—  In  urine  containing  a  large 
amount  of  indican,  uroglaucine^  or  indigotine,  may  be  found  as  a 
deposit.  It  presents  under  the  form  of  scales  or  needles  of  a 
bluish  colour. 

Haematoidine.  —  Ebstein  and  other  observers  have  found 
haematoidine  in  certain  urinary  deposits,  especially  in  cases  of 
pyelitis  in  pregnancy,  in  amyloid  a 
degeneration  of   the  kidneys,   in  Wk  S 


crystals  (Fig.  72).    These  crystals  Fig.  72.— Crystals  of  Hjsma- 


surface  of  tube-casts,  and  bladder  and  renal  epithelium.  They 
are  of  a  yellowish  or  reddish-brown  colour,  and  are  distinguished 
from  bilirubine,  with  which  they  are  apt  to  be  confounded,  by 
a  transient  blue  colour  which  contact  with  nitric  acid  imparts  to 
them. 


scarlatinal  nephritis,  in  typhoid 
fever,  in  cancer  of  the  kidneys,  and 
cancer  of  the  bladder.  Haematoi- 
dine is  the  product  of  decomposi- 
tion of  the  blood,'  and  is  found  in 
cases  of  blood  extravasation  of 
long  standing.  Microscopic  exami- 
nation shows  it  in  the  form  of 
acicular,  or  sometimes  rhomboidal, 


are  often  found  deposited  on  the 


TOIDINE. 


Fig.  73. 


Cholesterine  is  sometimes  found  as  a  urinary  deposit  in  cases 
of  chyluria  and  fatty  degeneration  of  the  kidneys  (vide  p.  194). 

15 


CHAPTEE  VII. 


TO  DETERMINE  THE  CHEMICAL  COMPOSITION  OF 
A  CALCULUS. 

Pulverize  the  calculus,  and  heat  to  redness  in  a  platinum 
crucible.  The  powder  burns  completely,  and  leaves  hardly 
any  residue  (A). 

The  powder  blackens,  and  leaves  a  considerable  residue  (B). 

A.  The  calculus  is  composed  entirely  of  organic  substances. 

The  primitive  cal-  ' 
cuius  is  saturated      (a)  Treated  with  caustic 
with  nitric  acid,  and  potash,  nothing  is  evolved, 
after  evaporation  is-< 

treated    with  am-      (b)  Treated  with  potash, 
monia     (murexide  ammonia  is  evolved, 
reaction).  V 

/  (a)  The  nitric  solution 
evaporated  gives  a  yellow 
residue  on  cooling,  which  is 
coloured  by  potash  (cold) 
reddish-yellow,  and  heated, 
violet-red. 

(b)   The    nitric  solution" 
evaporated    gives    a  dark 

/  brown  residue ;  the  powder 
tion  with  ammonia,  (  ,.     ,      .        9      .  r    -.  . 

Al  • -,    dissolves  m  ammonia  and  m 

gives  the  murexide      ,    ,  •     i  1 

rea  tion  potash  ;  the  ammoniacal  solu- 

tion, acidified  by  acetic  acid, 
deposits  microscopic  hexa- 
gonal tubules  ;  dissolved  in 
potash,*  with  the  addition  of 
nitro-prussiate  of  soda,  a 
\  beautiful  violet  coloration  is 
\produced. 


The  nitric  solu- 
tion, after  evapora- 


Uric  acid. 

Urate  of 
ammonia. 


-Xanthine. 


>Cystine. 


CHEMICAL  COMPOSITION  OF  A  CALCULUS.  227 


The  powder  burns 
with  a  brilliant 
flame. 


Fibrine  or 
blood  clot. 


Bile  pig- 
ments. 


r    (a)  It  is  insoluble  in  potash.^ 
Treated  with  ether  it  gives  a 
solution  which  on  evaporation  rCholesterine. 
deposits   pearly  rhomboidal  | 
scales. 

(b)  During  the  heating  it  | 
evolves  a  burnt-horn  odour  ; 
it  is  insoluble  in  potash,  and  j 
^precipitable  by  acetic  acid. 
The  powder  treated  with  chloroform  gives  an 
orange-yellow  colour,  and  on  the  addition  of  nitric 
acid  gives  the  reaction  of  Gmelin. 

B.  The  primitive  poivder,  treated  with  nitric  acid  and 
ammonia,  gives  the  murexide  reaction ;  it  contains  urates 
with  fixed  base  (soda,  potash,  magnesia,  lime),  oxalate  of  lime, 
phosphate  of  lime,  carbonate  of  lime,  ammonio -phosphate  of 
magnesia, 

(1)  The  residue  is  easily  disintegrated  by  the  blow-pipe.  The 
primitive  powder  evolves  ammonia  on  being  treated  with  potash. 
Calcined  alone,  it  gives  off  an  ammoniacal  odour. 

It  dissolves  in  acetic  acid,  and  ammonia}  Ammonio.phos. 
Hmfform  " *  !  Phate  of  magnesia. 

(2)  The  residue  is  unaffected  by  the  blow-pipe, 

(a)  The  residue  is  white/ 
The  powder  does  not  effervesce 
either  before  or  after  calcina- 
tion. It  is  soluble  in  hydro- 
chloric acid,  and  is  precipi- 
tated from  this  solution  by 
ammonia.  It  also  dissolves 
in  acetic  acid;  the  acetic 
solution  gives,  with  oxalate  of 
ammonium,  a  precipitate  of 
^oxalate  of  lime.  j 

(b)  The  primitive  powder  \ 
is  unaffected  by  acetic  acid; 
it  is  dissolved  by  mineral 
acids  with  effervescence,  and 
is  precipitated  by  ammonia. 
The  alkaline  residue  effer- 
vesces with  acids. 

(c)  The  powder,  heated  for 
white  heat,  develops  an  in- 
tense white  flame ;  before 
calcination  it  effervesces  with 
acids.  It  is  precipitated  from 
a  neutralized  chlorhydric  solu- 

Ition. 


Non  -  alkaline 
residue. 


Basic  phos- 
phate of  lime. 


Alkaline  residue. 


Oxalate  of 
calcium. 


Carbonate 
lime. 


of 


228 


THE  UEINE  IN  HEALTH  AND  DISEASE. 


(3)  The  primitive  powder  gives  with  nitric  acid  and 
ammonia  the  uric  acid  reaction,  but  heated  to  redness  it 
leaves  a  residue. 


Residue  fusible 
by  the  blow-pipe. 


Residue  non-fus- 
ible by  the  blow- 
pipe. 


(a)  It  communicates  to  the 
flame  an  intense  yellow  colour. 

(b)  It  imparts  to  the  flame  \ 
a  violet  colour,  and  chloride  ( 
of  platinum  precipitates  it  f 
from  a  chlorhydric  solution.  ) 

f    (a)  After  calcination 
reactions  are  those  of  carbon 
ate  of  lime. 

(b)  It  dissolves  with  feeble  ^ 
effervescence  on  being  treated 
with  dilute  sulphuric  acid,  and 
is  precipitated  from  this  solu- 
tion by  phosphate  of  soda  and 
ammonia. 


its] 
on-  > 


Urate  of 
soda. 

Urate  of 
potassium. 

Urate  of 
lime. 


Urate  of 
magnesium. 


In  the  case  of  a  mixed  calculus,  with  different  layers  super- 
posed on  one  another,  the  following  process  is  to  be  observed  : 
Boil  the  calculus  in  a  little  distilled  water ;  filter,  and  separately 
collect  the  filtered  portion  (A)  ;  wash  the  residue  with  boiling 
water.  Boil  the  washed  residue  in  dilute  hydrochloric  acid,  and 
if  effervescence  result,  the  presence  of  carbonate  of  lime  is 
indicated.  Then  filter  the  acid  liquid.  Collect  the  filtered 
liquor  (B),  and  wash  the  residue,  if  any,  with  water. 

Aqueous  Solution  (A). — The  aqueous  solution  may  contain 
urate  of  ammonium,  urate  of  sodium,  and  urate  of  calcium. 
Evaporate  a  few  drops  of  this  solution  on  a  watch-glass,  and  if 
but  a  small  trace  of  residue  be  obtained,  allow  the  remainder  to 
repose,  and  regard  the  calculus  as  containing  only  an  appreciable 
quantity  of  alkaline  urates.  If,  on  the  contrary,  an  appreciable 
residue  is  obtained,  boil  about  a  fourth  of  the  solution  with  a 
little  caustic  potash.  Should  the  liquid  contain  ammonia,  this 
gas  is  evolved,  and  may  be  recognised  by  its  odour  and  other 
tests.  The  remainder  of  the  solution  is  reduced  by  evaporation 
to  a  small  volume,  a  little  concentrated  nitric  acid  is  added,  and 
evaporation  to  dryness  is  accomplished.  A  rose-coloured  residue 
becoming  red  by  the  addition  of  ammonia  indicates  the  presence 
of  uric  acid.    The  residue  is  incinerated  and  the  ash  dissolved 


CHEMICAL  COMPOSITION  OF  A  CALCULUS.  229 


in  water,  the  liquor  being  divided  into  two  portions.  Acidulate 
the  one  portion  with  acetic  acid,  and  add  a  drop  of  oxalate  of 
ammonia,  which  in  presence  of  calcium  produces  a  white  pre- 
cipitate. The  other  portion  is  acidulated  with  hydrochloric  acid 
and  evaporated  to  dryness.  The  presence  of  chloride  of  sodium 
is  manifested  by  small  cubical  crystals. 

Acid  Solution  (B).— This  solution  may  contain  chloride  of 
sodium  arising  from  the  decomposition  of  carbonate  or  oxalate 
of  calcium,  of  cystine,  of  phosphate  of  lime,  or  of  ammonio- 
magnesium-phosphate.  Add  dilute  ammonia  so  as  to  render 
the  solution  as  neutral  as  possible  without  affecting  its  trans- 
parency, and  then  a  little  acetate  of  ammonium,  which  causes  a 
white  precipitate  if  the  liquor  contains  oxalate  of  lime  or 
cystine.  The  latter  is  rarely  found  in  mixed  calculi,  and  is  easily 
separated  from  oxalate  of  lime  by  means  of  ammonia.  If  the 
acetate  of  ammonium  precipitates,  filter  and  add  an  excess  of 
oxalate  of  ammonium  to  the  filtered  liquid;  if  the  acetate  of 
ammonium  does  not  precipitate  directly,  treat  the  clear  liquid 
with  oxalate  of  ammonium  without  previous  filtration.  The 
presence  of  calcium  is  indicated  by  a  white  precipitate.  If 
necessary,  then  filter  and  add  ammonia  in  excess.  The  presence 
of  phosphoric  acid  and  magnesium  is  indicated  by  a  white 
precipitate.  If  no  precipitate  is  produced,  add  sulphate  of 
magnesia.  The  presence  of  phosphoric  acid  is  then  indicated  by 
the  deposit  of  a  white  crystalline  powder,  after  agitation  of  the 
liquid. 

Residue  (C.) — This  consists  of  uric  acid,  recognisable  as 
above. 

Sand  and  Gravel  are  analyzed  like  calculi.  They  should 
previously  be  submitted  to  microscopical  examination,  as  they 
may  present  physical  appearances  by  which  they  may  be  dis- 
tinguished. 


CHAPTER  VIII. 


MEDICAMENTS  AND  ACCIDENTAL  ELEMENTS  IN 
THE  URINE. 


Alcohol. 
Antipyrine. 

Antifebrine  (Acetanilide). 

Arsenic  and  Antimony. 

Alkaloids. 

Aristol. 

Bromides. 

Carbolic  Acid. 

Chloroform. 

Chloral. 

Chlorate  of  Potash. 

Iron. 

Iodides. 

Iodoform. 

Kairine. 

Lithia. 

Lead  and  Copper. 


Mercury. 
Naphthaline. 

Naphthol  and  other  Phenols. 

BethoL 

Phenacetine. 

Salicylates. 

Salol. 

Saccharine. 

Strontium. 

Tannin. 

Turpentine. 

Rhubarb. 

Santonine. 

Thalline. 

Urethan. 

Filaments  of  Tissues ; 
Grains  of  Starch. 


Alcohol. — The  greater  portion  of  the  alcohol  taken  into  the 
system  is  changed  by  oxidation  into  carbonic  acid  and  water, 
and  consequently,  when  imbibed  in  large  quantities,  is  found 
only  in  diminished  quantity  in  the  urine.  This  portion,  however, 
may  be  separated  from  the  urine  by  a  process  of  distillation. 
About  100  c.c.  of  urine  are  to  be  distilled  in  a  glass  retort  with  a 
refrigerating  apparatus.  If  to  a  few  drops  of  the  product  of 
distillation  a  few  drops  of  a  dilute  solution  of  bichromate  of 
potash  and  dilute  sulphuric  are  added,  and  heat  applied,  if  the 
urine  contain  alcohol,  the  original  yellow  colour  passes  into 
green  in  consequence  of  the  reduction  of  chromic  acid  to 
chromic  oxide,  while  simultaneously  an  odour  of  aldehyde  is 


MEDICAMENTS  AND  ACCIDENTAL  ELEMENTS  IN  URINE.  231 


evolved.  Otherwise  (xanthogen  reaction),  the  product  of  the 
distillation  of  the  urine,  once  or  twice  rectified,  is  mixed  with 
a  little  caustic  potash  and  a  few  drops  of  sulphide  of  carbon ; 
after  agitation,  an  equal  volume  of  water  is  to  be  added,  and  a 
drop  of  sulphate  of  copper  solution.  If  any  alcohol  is  present, 
a  yellow  precipitate  of  xanthogenate  of  copper  forms. 

The  reaction  of  Leben  may  also  be  applied,  as  in  the  case  of 
acetone  (vide  Acetone). 

Antipyrine.  —  The  frequent  use  of  antipyrine  renders  its 
presence  in  the  urine  of  clinical  significance,  and  especially  in 
its  behaviour  towards  the  usual  albumen  and  sugar  reagents. 

Polarimetric  Examination. — Feeble  or  concentrated  solution 
of  antipyrine  does  not  affect  the  plane  of  polarization.  It  is 
otherwise  with  the  antipyrine  which  has  traversed  the  economy, 
and  which  has  doubtless  thus  undergone  some  change  ;  it  deviates 
the  plane  of  polarization  to  the  left. 

Nitric  acid  does  not  affect  antipyrine,  but  Tanret's  solution 
(vide  Albumen,  p.  126)  gives  a  precipitate  readily  soluble  in 
alcohol,  and  on  being  heated.  The  precipitate  formed  with 
peptones  and  alkaloids  is  even  more  soluble. 

EsbacJi's  reagent  likewise  precipitates  antipyrine. 

M  elm's  reagent  gives  a  precipitate  of  antipyrine  very  soluble 
in  alcohol,  and  on  application  of  heat,  reappearing  when  the 
liquid  cools. 

F  err  o  cyanide  of  potassium  and  acetic  acid  solution  is  without 
effect  on  antipyrine.  To  be  absolutely  certain  of  the  presence  of 
albumen,  five  tests  must  be  applied,  thus : 


Rota- 
tory 
Power. 

Nitric 
Acid. 

Tanret's 
Solution. 

Esbach's 
Solution. 

Menu's 
Reaction. 

Ferrocy. 
Potass, 
and  Acet. 
Acid. 

Albumen  - 

Stable 

Stable 

Precip. 

Precip. 

Precip. 

precip. 

precip. 

stable 

stable 

stable 

Antipyrine 

0 

Precip. 

Precip. 

Precip. 

0 

soluble 

soluble 

soluble 

(«)by 

(«)  by 

(«)by 

heat, 

heat, 

heat, 

(6)  by 

(6)  by 

(b)  by 

alcohol 

alcohol 

alcohol 

Alkaloids 

0 

0 

Do. 

Do. 

Do. 

0 

Peptones  - 

0 

0 

Do. 

Do. 

Do. 

0 

232 


THE   URINE  IN  HEALTH  AND  DISEASE. 


Having  separated  the  albumen  by  heat,  the  presence  of  anti- 
pyrine  may  be  demonstrated  by  means  of  perchloride  of  iron 
and  Tanret's  solution.  The  action  of  the  perchloride  of  iron 
must  not  be  confounded  with  the  violet  coloration  due  to  the 
presence  of  salicylates  in  the  urine  (vide  Salicylates,  p.  237). 
Having  proved  the  absence  of  salicylates,  it  may  be  concluded 
that  the  red  coloration  produced  by  the  perchloride  is  due  to 
antipyrine. 

In  this  operation  it  is  indispensable  that  the  urine  be  not 
treated  with  subacetate  of  lead,  as  the  presence  of  acetates 
occasions  with  the  perchloride  of  iron  the  same  colour  as  does 
antipyrine. 

If  the  urine  be  decolorized  by  a  20  per  cent,  solution  of 
nitrate  of  lead,  and  ferric  chloride  be  added,  a  precipitate  of 
chloride  of  lead  is  obtained. 

Antipyrine  causes  a  partial  decoloration  of  Fehling's  solution, 
the  colour  of  the  reagent  passing  from  yellow  to  violet-gray. 
Antipyrine  therefore  interferes  with  Fehling's  test  in  the 
presence  of  sugar.  On  treating  urine  containing  antipyrine, 
and  adding  a  few  drops  of  fuming  nitric  acid,  a  green  coloration 
is  produced,  which  becomes  red  with  an  excess  of  the  acid. 

Antifebrine. — The  presence  of  antifebrine  is  thus  revealed : 
The  urine  is  mixed  with  a  fourth  of  its  volume  of  concentrated 
sulphuric  acid  and  boiled  for  a  few  minutes.  On  cooling,  a 
few  drops  of  carbolic  acid  or  hypochlorite  of  lime  are  added. 
If  antifebrine  be  present,  the  solution  becomes  red  on  the 
addition  of  nitric  acid.  Subsequently  it  becomes  of  a  beautiful 
blue  colour  (iodophenol  reaction).  If  the  urine  be  agitated  with 
chloroform,  and  evaporated,  and  the  residue  be  heated  with 
nitrate  of  mercury,  a  green  coloration  is  the  result,  in  which 
traces  of  acetanilide  exist. 

Arsenic  and  Antimony. — Destroy  the  organic  matters  with 
chlorate  of  potash  and  hydrochloric  acid.  Evaporate  until  the 
complete  expulsion  of  the  chlorine ;  wash  the  residue  with  water ; 
evaporate  the  filtered  liquid  to  a  third  of  its  volume,  and  test  for 
the  metals  by  Marsh's  method. 

Alkaloids. — The  animal  alkaloids  found  in  the  urine  are  of 
two  varieties,  viz.:  (i)  The  ptomaines,  which  develop  in  dead 


MEDICAMENTS  AND  ACCIDENTAL  ELEMENTS  IN  URINE.  233 

matter  on  putrefaction ;  (2)  the  leucomaines,  which  are  ex- 
creted during  life.  These  alkaloids  are  distinguished  from 
alkaloids  of  vegetable  origin  by  the  Brouardel-Boutiny  re- 
action (ferrocyanide  of  potassium  and  perchloride  of  iron). 
Vegetable  alkaloids  have  no  effect  on  this  reagent,  while  leuco- 
maines on  contact  with  it  cause  an  intense  blue  coloration, 
morphia  alone  giving  an  intense  reaction,  and  atropia  a  feeble 
one. 

The  solution  of  Von  Jaksch — 

Potass.  Iod.         ...       ...       ...       ...    10  grammes 

Iodine    5  ,, 

Water   10  ,, 

— gives  a  green  fluorescence  on  contact  with  leucomaines. 

Vegetable  Alkaloids.  —  Tanret's  solution  forms  the  most 
delicate  test  for  vegetable  alkaloids.  It  gives  a  white  precipi- 
tate, which  disappears  on  the  application  of  heat  or  the  addition 
of  alcohol. 

Trichloracetic  Acid,  which  is  sometimes  employed  as  an 
albumen  reagent,  precipitates  alkaloids  when  concentrated. 
This  precipitate  is  dissolved  by  the  addition  of  water,  by  heat, 
by  the  addition  of  alcohol,  and  by  an  excess  of  the  reagent. 

The  frequent  administration  of  quinine  as  a  therapeutic 
agent  renders  its  presence  in  the  urine  important.  When  the 
residue  of  the  evaporation  with  ether  is  treated  with  a  drop  of 
sulphuric  acid,  a  marked  blue  fluorescence  is  an  excellent  test  of 
quinine.  The  acid  liquid  gives  the  following  further  character- 
istic reactions  of  quinine  :  Chlorinated  water  and  ammonia,  a 
green  colour  ;  chlorinated  water  with  one  drop  of  a  solution  of 
ferrocyanide  of  potassium  and  ammonia,  a  red  colour. 

Instead  of  chlorinated  water,  which  is  very  unstable,  the 
liquor  of  Labarraque  may  be  employed. 

Aristol  is  eliminated  in  the  urine  under  the  form  of  an 
alkaline  iodide  and  of  thymol.  Its  presence  must  be  demon- 
strated by  the  tests  employed  for  these  agents. 

Bromides. — The  action  of  chlorides  on  bromides  being  fre- 
quently obscured  by  organic  matters,  the  following  process 
recommended  by  M.  Bruneau  should  be  followed.    Heat  gently 


234  THE  UEINE  IN  HEALTH  AND  DISEASE. 


in  a  test-tube,  and  agitate.  Chlorine  gas  is  given  off.  To  the 
aqueous  solution  add  a  little  chloroform  or  sulphide  of  carbon ; 
agitate,  and  allow  to  repose.  Bromine  is  indicated  by  the  chloro- 
form which  rests  below  the  urine  assuming  a  deep  reddish- 
yellow  colour,  which  disappears  on  agitation  with  potash  or  soda. 

Carbolic  Acid  appears  in  the  urine  after  the  internal 
administration  of  this  drug  in  the  form  of  phenyl-sulphate  of 
potash.  To  demonstrate  its  presence,  add  a  little  hydrochloric 
acid  to  the  urine  and  distil.  To  the  distillate  add  bromine 
water,  when  a  precipitate  of  tribromophenol  is  obtained.  With 
perchloride  of  iron  a  blue  coloration  is  produced.  With 
Millon's  reaction  a  red  colour  is  obtained.  A  drop  of  aniline 
and  a  few  c.c.  of  the  liquor  of  Labarraque  give  a  blue  colora- 
tion, which  appears  slowly,  but  which  lasts  many  weeks. 

Chloroform. — As  the  presence  of  chloroform  in  urine  is  a 
contested  point,  its  mode  of  detection  need  not  be  described. 

Chloral. — Chloral  is  not  naturally  eliminated,  nor  in  the 
form  of  chloroform.  Its  ultimate  products  are  carbonic  acid 
and  urochloralic  acid.    The  latter  reduces  Fehling's  solution. 

Chlorate  of  Potash. — This  salt  is  entirely  eliminated  by  the 
urine.  To  demonstrate  its  presence,  add  to  the  urine  a  few  drops 
of  sulphate  of  indigo,  dilute  sulphuric  acid,  and  a  solution  of 
sulphate  of  soda.  The  blue  colour  instantly  disappears  in 
presence  of  chlorate  of  potash. 

Iron. — The  presence  of  iron  is  easily  demonstrated  in  the 
urine.  Add  a  few  drops  of  nitric  acid,  and  boil.  Peroxide  of 
iron  is  thus  produced.  Add  a  solution  of  ferrocyanide  of 
potassium,  when  the  characteristic  coloration  of  Prussian  blue 
appears. 

Iodides. — Iodides  pass  rapidly  into  the  urine.  To  demon- 
strate their  presence,  add  a  few  grains  of  starch.  Agitate  with 
freshly-prepared  chlorine  water,  or  one  or  two  drops  of  fuming 
nitric  acid.  The  iodine  thus  set  free  assumes  a  beautiful 
characteristic  blue  colour.  An  excess  of  nitric  acid  must  be 
avoided.  In  place  of  nitric  acid  or  chlorinated  water,  an  alka- 
line hypochlorite,  or  perchloride  of  iron  may  be  employed. 

Test  for  Iodine  in  Urine  {Journal  de  Medicine  de  Paris, 
September  23,  1888).— To  10  c.c.  of  urine  add  2  c.c.  of  dilute 


MEDICAMENTS  AND  ACCIDENTAL  ELEMENTS  IN  UBINE.  235 

sulphuric  acid  (one  part  to  five  of  water)  ;  then  add  five  drops 
of  solution  of  starch  freshly  prepared.  To  this  mixture  add, 
drop  by  drop,  a  1  per  cent,  solution  of  nitrate  of  potash, 
shaking  the  vessel.  If  the  urine  contain  iodine,  the  addition 
of  the  first  few  drops  will  produce  a  violet  or  more  or  less 
intense  blue  coloration,  which  will  disappear  on  the  addition 
of  a  drop  of  10  per  cent,  solution  of  hyposulphite  of  soda. 
The  addition  to  the  urine  of  a  few  drops  of  sulphuret  of  carbon 
intensifies  the  reaction. 

Iodoform  may  be  found  in  the  urine  after  the  administration 
of  this  drug.  Agitate  the  urine  with  ether ;  spontaneous  evapo- 
ration leaves  iodoform  as  a  residue.  It  is  characterized  by  its 
odour,  and,  microscopically,  by  its  hexagonal  scales. 

Kairine. — A  drop  of  perchloride  of  iron  solution  gives,  with 
kairine,  a  violet  colour,  which  rapidly  turns  into  brown. 
Bichromate  of  potash  gives  a  violet  pigment  which,  with 
alcohol,  gives  a  mauve  solution.  The  addition,  drop  by  drop,  of 
a  10  per  cent,  solution  of  chloride  of  lime  to  urine  acidified  by 
acetic  acid,  and  containing  kairine,  gives  a  fuchsine  colour. 

Lithia. — Calcine  completely  a  certain  quantity  of  urine  so  as 
to  obtain  a  white  ash,  which  dissolve  in  dilute  hydrochloric  acid. 
Filter  the  liquid,  evaporate  to  dryness,  and  dissolve  in  equal 
parts  of  ether  and  absolute  alcohol.  Evaporate  the  alcoholic 
liquor  to  dryness,  and  test  the  residue  with  the  blow-pipe.  If 
it  contain  lithia,  a  red  flame  is  the  result.  Spectroscopic  examin- 
ation reveals  characteristic  rays. 

Lead  and  Copper. — Evaporate  the  urine  to  dryness,  and  car- 
bonize the  residue  at  as  low  a  temperature  as  possible.  Ignite  in 
a  porcelain  capsule,  and  moisten  from  time  to  time  with  concen- 
trated nitric  acid.  On  cooling  treat  the  ash  with  water  acidulated 
with  a  few  drops  of  nitric  acid,  filter,  and  test  the  filtrate  for  lead 
and  copper.  With  lead  sulphuretted  hydrogen  gives  a  black  or 
dark-brown  precipitate,  sulphuric  acid  a  white  precipitate,  and 
chromate  of  potash  a  yellow  precipitate.  If  the  urine  contain 
copper  it  presents  a  bluish  colour,  if  the  quantity  is  not  ex- 
tremely feeble ;  with  sulphuretted  hydrogen  a  black  or  brown 
colour  results ;  ammonia  gives  a  greenish-blue  precipitate,  which 
dissolves  in  an  excess  of  the  reagent,  giving  an  azure  blue 


236 


THE  UKINE  IN  HEALTH  AND  DISEASE. 


colour ;  and  ferrocyanide  of  potassium  gives  a  brown  or  reddish- 
brown  colour. 

Mercury. — Acidulate  the  urine  with  hydrochloric  acid,  and 
add  powdered  zinc,  which  precipitates  all  the  mercury.  Wash 
the  precipitate  with  hot  water,  then  with  alcohol  and  ether,  and 
treat  after  Ludwig's  method.  Secondly,  acidulate  the  urine 
with  hydrochloric  acid  and  heat.  Cool,  and  heat  anew. 
Plunge  into  the  liquid  several  times  a  thin  metallic  plate  com- 
posed of  copper  and  zinc,  on  which  the  mercury  deposits.  Wash 
the  plate,  and  expose  to  iodine  vapour,  when  iodide  and  biniodide 
of  mercury  are  formed ;  or  treat  the  plate  after  Marsh's  method. 

Naphthaline. — If  to  urine  containing  naphthaline  a  few  drops 
of  ammonia  be  added,  or  soda,  a  beautiful  blue  colour  results. 
When  naphthaline  is  administered  as  a  drug  the  urine  becomes 
of  a  characteristically  dark  colour. 

Naphthol  and  other  Phenols. — Treat  a  given  quantity  of 
urine  with  half  its  volume  of  chloroform,  agitate  gently,  and 
pour  into  a  decantation  apparatus.  The  decanted  chloroform  is 
received  in  a  test-tube,  and  a  pastil  of  caustic  potash  is  added. 
Characteristic  coloured  spots  result,  varying  with  the  nature 
of  the  phenol  (Desquelle,  Repertoire  de  Pharmacie,  1890, 
p.  101). 

With  ordinary  phenol,  a  rose  colour. 
With  thymol,  a  deep  violet  colour. 
With  resorcine,  a  rose  colour. 
With  hydroquinon,  a  golden  yellow  colour. 
With  naphthol  (x),  a  sky-blue  colour. 
With  naphthol  (b),  a  greenish-blue. 
With  pyrogallol,  a  violet  colour. 
With  creosote,  a  violet  colour. 
With  guaiacol,  a  rose-violet  colour. 
Yvon  commends  the  subjoined  as  naphthol  tests : 

(i.)  Acid  nitrate  of  mercury   5  grammes. 

Nitric  acid    ...       ...       ...       ...       ...  15  ,, 

(ii.)  Saturated  solution  of  nitrate  of  potash  ...  10  ,, 
Sulphuric  acid       ...       ...       ...       ...    5  ,, 

These  two  tests  give  with  naphthol  a  red  colour. 


MEDICAMENTS  AND  ACCIDENTAL  ELEMENTS  IN  UEINE.  237 

Bethol,  or  Salicylate  of  Naphthol. — Bethol  is  eliminated  in 
the  urine  as  naphthol,  and  salicylic  and  salicyluric  acids. 

Grenouillet  (Bepertoire  de  Pharmacie,  1890,  p.  470)  recom- 
mends the  following  process  for  its  isolation :  Eeduce  500  c.c.  of 
urine  to  the  volume  of  150  c.c. ;  after  cooling,  filter,  and  agitate 
the  liquid  with  its  volume  of  ether.  Evaporate,  and  dissolve  the 
residue  in  boiling  water.  After  cooling,  salicylic  acid  is  revealed 
by  perchloride  of  iron  (vide  Salicylates). 

Otherwise  add  to  the  urine  2  per  cent,  of  sulphuric  acid  and 
distil.  Agitate  the  distilled  product  with  chloroform.  This 
liquor  gives  with  caustic  potash  the  characteristic  blue  colour  of 
naphthol. 

Phenacetine. — Strongly  acidulate  the  urine  with  hydrochloric 
acid,  and  heat.  On  cooling  add  from  one  to  two  drops  of  a  per- 
chloride of  iron  solution,  when  a  reddish- brown  coloration  is 
produced.  Or  to  2  c.c.  of  urine  of  an  acid  reaction  add  from  four 
to  five  drops  of  a  solution  of  chromic  acid  (3  per  cent.).  At  the 
point  of  contact  of  the  two  fluids  a  brown  coloration  appears. 

Salicylates. — A  few  drops  of  a  solution  of  perchloride  of  iron 
cause  a  violet  coloration  in  urine  containing  a  salicylate ;  but 
if  the  salicylate  exist  in  feeble  proportion,  and  the  urine  con- 
tain a  large  proportion  of  phosphates,  a  precipitate  of  phosphate 
of  iron  forms,  which  obscures  the  salicylate  reaction.  In  this 
case  the  salicylic  acid  must  be  isolated.  To  accomplish  this,  add 
to  100  c.c.  of  urine  from  six  to  eight  drops  of  hydrochloric  acid, 
and  agitate  gently  with  6  c  c.  of  ether.  After  sufficient  repose 
the  ether  is  decanted  and  poured  out  on  a  saucer  containing  a 
few  drops  of  a  10  per  cent,  solution  of  perchloride  of  iron. 
After  evaporation  of  the  ether  a  beautiful  violet  coloration 
ensues. 

Salol,  or  salicylate  of  phenol,  is  not  normally  voided  with  the 
urine.  The  derivatives  of  salol  reduce  Fehling's  solution,  and 
deviate  the  plane  of  polarization  to  the  left.  To  distinguish 
glucose  in  presence  of  salol,  the  urine  decolourized  by  a  tenth 
part  of  its  volume  of  subacetate  of  lead  is  placed  in  a  tube  with 
5  centigrammes  of  hydrochlorate  of  phenylhydrazine  and  0'20 
of  pure  soda.  The  liquid  becomes  of  a  yellow  colour,  and  is 
heated  for  half  an  hour  on  a  water-bath.    It  is  then  poured  into 


238 


THE  URINE  IN  HEALTH  AND  DISEASE. 


a  suitable  glass  vessel  and  cooled,  when,  if  it  contain  sugar, 
a  crystalline  deposit  results,  recognisable  by  the  microscope.  "With 
salol  the  deposit  is  amorphous. 

Saccharine. — Agitate  the  urine  with  a  few  drops  of  sulphuric 
acid,  and  then  with  a  mixture  of  ethylic  and  petrolic  ether. 
Evaporate  the  ethereal  liquid,  and  dissolve  the  residue  in  a  little 
hot  water.  The  solution  possesses  a  sugary  sweetness  most 
marked  in  the  case  of  saccharine.  Neutralize  the  residue  with 
carbonate  of  soda,  and  treat  with  a  small  excess  of  nitrate  of 
mercury.  A  saccharinate  of  mercury  results,  which  may  after 
washing  be  collected  and  dried  on  a  filter.  Place  this  in  a  test- 
tube,  and  add  twice  its  volume  of  resorcine.  Add  a  few  drops  of 
sulphuric  acid,  and  heat.  Divers  colours  result,  the  mass  becomes 
resinous,  and  gives  off  sulphurous  acid.  Allow  the  remainder  to 
cool,  dilute  with  water,  and  saturate  with  potash  or  caustic 
soda.  There  results  a  reddish-brown  liquid  with  green  fluor- 
escence. This  fluorescence  becomes  manifest  if  a  few  drops  of 
the  liquid  be  added  to  a  tube  containing  water. 

Strontium. — The  urine  concentrated  to  a  tenth  of  its  volume 
is  filtered  after  cooling.  To  a  portion  of  it  which  is  perfectly 
limpid,  a  few  drops  of  neutral  chromate  of  potash  solution  are 
added.  If  there  be  no  result,  it  may  be  inferred  that  no  salts  of 
barium  are  present.  To  another  perfectly  limpid  portion  of 
urine  a  few  drops  of  sulphuric  are  added.  A  precipitate  of 
sulphate  of  strontium  is  formed.  Ignite  with  carbon,  and  a 
transformation  into  sulphide  takes  place.  Dissolve  the  residue 
in  hydrochloric  acid,  and  examine  for  strontium  spectroscopi- 
cally. 

Tannin. — Tannin  is  eliminated  in  the  urine  in  the  form  of 
gallic  acid.  With  perchloride  of  iron,  gallic  acid  in  urine  gives 
a  black-blue  precipitate.  Alkalies  give  a  brown  and  black 
colour. 

Turpentine  with  protochloride  of  antimony  gives  a  red 
colour;  and  M.  Loison  (Bejp.  de  Pharm.,  1890)  recommends  the 
following  test  process :  Evaporate  500  c.c.  of  urine  on  a  water- 
bath  to  the  consistence  of  an  extract.  To  the  residue  add  10  c.c. 
of  boiling  alcohol,  filter,  and  reduce  by  evaporation  to  5  c.c. 
Add  to  these  5  c.c.  a  few  drops  of  hydrochloric  acid,  and  place 


MEDICAMENTS  AND  ACCIDENTAL  ELEMENTS  IN  URINE.  239 

in  a  fine  tube  containing  some  crystals  of  proto chloride  of 
antimony.-  Gently  heat  the  tube,  and  after  a  minute's  boiling, 
if  the  urine  contain  turpentine,  an  intense  red  colour  appears. 

Rhubarb. — After  partaking  of  rhubarb,  a  deep  yellow  colour 
is  imparted'  to  the  urine,  sometimes  resembling  the  urine  of 
jaundice.  The  addition  of  an  alkali  to  such  urine  causes  a  red 
colour.  The  following  reactions  distinguish  rhubarb  from 
santonine  :  In  the  case  of  rhubarb,  senna,  etc.,  the  coloration 
produced  by  the  alkali  persists  for  more  than  twenty -four 
hours.  The  coloration  appears  promptly  with  soda  or  ammonia. 
Eeducing  agents,  such  as  powder  of  zinc  and  sodium,  cause  the 
colour  to  disappear.  Baryta  solution  and  lime-water  precipitate 
the  colouring  matter. 

Santonine. — The  coloration  caused  by  alkalies  does  not  persist 
beyond  twenty-four  hours,  and  is  slow  to  appear.  Eeducing 
agents  do  not  cause  the  colour  to  disappear.  Baryta  and  lime- 
water  do  not  precipitate  the  pigment,  and  the  liquid  becomes 
limpid  on  repose,  but  the  red  colour  persists. 

If  the  urine  be  acidified  with  sulphuric  acid  and  agitated  with 
amylic  alcohol,  no  coloration  results  in  the  case  of  santonine, 
while  in  the  presence  of  rhubarb  a  yellow  colour  is  the  result. 

Thalline. — Urine  containing  thalline  exhibits  a  brownish  tint 
with  greenish  reflection.  To  identify  its  presence,  treat  the  urine 
with  chloroform  or  with  ether,  decant,  and  evaporate  in  a  porcelain 
crucible,  when  contact  with  perchloride  of  iron  will  give  a  beau- 
tiful green  colour. 

Urethan. — Agitate  500  c.c.  of  urine  with  a  sufficient  quantity 
of  ether.  Decant,  wash  with  distilled  water,  and  completely 
evaporate.  Add  to  from  10  to  20  c.c.  an  excess  of  potash.  To 
this  add  a  solution  of  perchloride  of  mercury,  when  a  more  or 
less  abundant  white  precipitate  is  obtained. 

Filaments  of  Tissues  ;  Grains  of  Starch. — These  bodies  are 
easily  recognised  by  their  chemical  and  microscopic  characters. 
Cotton  fibres  are  coloured  blue  by  iodine  and  sulphuric  acid. 
Starch  gives  a  characteristic  blue  colour  with  a  solution  of 
iodine. 


APPENDIX. 


Conversion  of  Grammes  into  Grains  and  Vice  Versa. 


Grammes  to  Grains. 

1  =  15-43235 

2  =  30-86470 
3=  46-29705 
4  =  61-72940 
5=  77*16175 
6=  92-59410 

7  =  108-02645 

8  =  123-45880 

9  =  138-89115 


Grains  to  Grammes  and  Milligrammes. 


1 

=  0-6480 

or  64-80 

o 

-0-12958 

„  129-58 

3 

=  0-19437 

„  194  37 

4 

=  0  25916 

„  259-16 

5 

=  0-32395 

„  323-95 

6 

=  0-38874 

„  388-74 

7 

=  045353 

„  453-53 

8 

=  0-51832 

„  518-32 

9 

=  0-58311 

„  583-11 

Comparison  of  Measures  (English  into  Metric). 

1  minim  =0*5916  c.c. 

1  fluid  drachm  =  3*5495  c.c. 

1  fluid  ounce   =28*396  c.c. 

1  pint  =567*92  c.c.  =  0*56792  litre. 

1  quart  =1'3584  litre. 

1  cubic  inch    =16*386  c.c. 


Comparison  of  Weights  (Metric  into  English). 

1  milligramme  =0*01543  grain  (  =  nearly  the  ^th) 

1  centigramme  =  0*15432  grain 

1  decigramme  =1*54323  grains 

1  kilogramme  =35*27395  ounces  (Avoirdupois) 

or  2*2046213  lbs.  (Avoirdupois) 


APPENDIX. 


241 


To  convert  grammes  per  litre  into  grains  per  gallon,  multiply  by  70. 
To  convert  grains  per  gallon  into  grammes  per  litre,  multiply  by 
0-014286. 

To  convert  grammes  per  fluid  drachm  into  grains  per  fluid  ounce, 
multiply  by  123-46. 

1  millimetre  =  0*03937  inch 
25*4  mm.     =1  inch 

Johnson's  '  Analyst's  Laboratory  Companion.' 

To  convert  degrees  of  Fahrenheit's  thermometer  into  those  of  the 
Centigrade  scale,  subtract  32  and  multiply  by  % ;  and  conversely  to 
convert  Centigrade  readings  to  Fahrenheit  scale,  multiply  by  §  and 
add  32. 


16 


I  N  D 


E  X. 


A. 

Acetanilide,  elimination  of,  232 
Acetone,  183 

pathological  significance  of,  185 

properties  of,  183 

tests  for,  184 
Acetonuria,  185 

forms  of,  186 
Acid,  acetic,  187 

acetylacetic,  184 

benzoic,  93 

butyric,  187 

carbolic,  96 

carbonic,  117 

cholalic,  192 

choleic,  192 

cholic,  193 

formic,  187 

glycocholic,  192 

hippuric,  83-86 

lactic,  187 

omicholic,  99 

oxalic,  93 

oxaluric,  91 

phenic,  96 

phosphoglyceric,  110 

phosphoric,  107 

propionic,  187 

saccharic,  160 

salicylic,  237 

succinic,  92 

sulphuric,  105 

tannic,  41 

taurocholic,  192 

uric,  70 

valerianic,  187 
Acidity  of  urine,  32 
Agnosti's  reaction,  167 
Albumen,  118 

coagulation  of,  by  heat,  121 

coagulation  of,  by  nitric  acid,  123-125 

nitro-prussiate  of  soda,  test  for,  130 

picric  acid,  test  for,  127 

potassium  ferrocyanide,  test  for,  128 

Roch's  test  for,  131 

Spiegler's  test  for,  131 


Albumen,  Stutz's  test  for,  131 
Tanret's  test  for,  126 
quantitative  analysis  of,  136-145 
pathological  significance  of,  145-155 
therapeutic  indications  of,  146 

Alcohol,  elimination  of,  230 

Alkalinity  of  urine,  36 

Alkaloids,  cadaveric,  152 

Alkaptone,  96 

Allantoine,  91 

Alloxan,  73 

Almen's  sugar  test,  166 
Ammonia  in  urine,  115 
Amylamine,  182 
Antifebrine,  elimination  of,  232 
Antimony,  elimination  of,  232 
Antipyrine,  elimination  of,  231 
Aristol,  elimination  of,  233 
Arsenic,  elimination  of,  232 
Ascaris  lumbricoides,  213 

B. 

Bacillus  of  tuberculosis,  213 
Bacillus  urese,  214 
Bile,  elements  of,  188 
Bilharzia  haematobia,  213 
Bilifuscine,  190 
Bilihumine,  190 
Biliprasine,  189 
Bilirubine,  188 
Biliverdine,  189 
Biuret  reaction,  152,  153 
Blood-corpuscles  in  urine,  205 
Bodo  urinarius,  213 
Bromides,  elimination  of,  233 
Butyric  acid,  187 

C. 

Calculi,  analysis  of,  226 

of  carbonate  of  lime,  227 
of  cholesterine,  227 
of  cystine,  226 
of  oxalate  of  lime,  227 
of  phosphate  of  ammonia  and  mag- 
nesia, 227 


INDEX. 


243 


Calculi  of  ammonium  urate,  226 

of  calcium  urate,  228 

of  magnesium  urate,  228 

of  potassium  urate,  228 

of  sodium  urate,  228 

of  uric  acid,  226 

of  xanthine,  226 

urinary,  226 
Cells,  epithelial,  of  the  kidney,  210 

of  the  ureter,  210 

of  the  urethra,  211 

of  the  vagina,  210 
Cercomonas  urinarius,  213 
Chloral,  elimination  of,  234 
Chloride  of  sodium,  103 

analysis  of,  104 

pathological  significance  of,  105 

properties  of,  103 
Chloride  of  zinc  and  creatine,  87 

of  creatinine,  88 
Chlorides,  103  ' 

of  calcium,  103 

of  magnesium,  103 

of  potassium,  103 
Chloroform,  elimination  of,  234 
Cholesterine,  193,  194 

analysis  of,  194 

calculi  of,  227 
Colour  of  urine,  25 
Concretions,  215 
Copaiba  in  urine,  126 
Corpuscles  of  blood  in  urine,  205 
Creatine,  86 
Creatinine,  86 

analysis  of,  90 

extraction  of,  88 

variations  of,  90 
Crismer's  sugar  test,  165 
Cylinders  or  casts,  196 

amyloid,  197 

blood,  199 

epithelial,  194 

fatty,  197 

granulo-fatty,  197 

hyaline,  197 

mucous,  198 

prostatic  or  spermatic,  199 

pathological  significance  of,  199 
Cylindroids,  198 
Cystine,  179 

analysis  of,  180 

calculi  of,  226 

properties  of,  179 

sediments  of,  217 

sediments  (gravel),  229 

D. 

Day's  test  for  pus,  209 

Degree  of  acidity  of  urine,  32,  33 

of  alkalinity  of  urine,  36 
Density  of  urine,  31 

estimation  of,  31 

variations  in,  30 
Dextrine,  159 


Dextrose,  159 
Diabetes,  158 

glycopolyuric,  82 

insipidus,  158 

saccharine,  156 

toxic,  174 
Diathesis,  oxalic  acid,  95 

phosphatic,  113 

uric  acid,  82 
Distoma  haematobium,  13 
Diuretics,  action  of,  22 
Dumb-bell  crystals,  94 
Dyslisine,  193 

E. 

Bchinococci  in  urine,  213 

Ehrlich's  reaction,  192 

Elements,  accidental,  in  urine,  230 

of  the  bile  in  urine,  194 

organic,  in  urine,  203-214 

pathological,  in  urine,  196  200 
Epithelium  in  urine,  209-211 
Esbach's  tubes,  144 
Excretion  of  urine,  17 

mechanism  cf,  17-22 

F. 

Fat,  195 

Fehling's  sugar  test,  163 
Ferrein,  pyramids  of,  9 
Ferrocyanide  of  potassium  test  for  albu- 
men, 128 
Fibrine  in  urine,  150 
Filaria  sanguinis  hominis,  195,  213 
Fluorescence  of  urine,  27 

G. 

Galacturia,  195 
Gases  in  urine,  117 
Gerrard's  glycosometer,  172 
Globinuria,  148 

Globules  of  blood  in  urine,  205 

of  pus  in  urine,  208 
Globuline,  147 

analysis  of,  148,  149 

pathological  significance  of,  150 
Glucose,  158 

extraction  of,  161 

properties  of,  160 

tests  for,  161,  168 
Glycochole,  45,  192 
Glycocholic  acid,  192 
Glycosuria,  159 

alimentary,  159 

pathological  significance  of,  173 
physiological,  159 
simulated,  176 

therapeutic  indications  in,  176 

toxic,  159 
Gmelin's  reactionjfor  bile,  190 
Gravel,  forms  of,  216-225 
Guaiacum  as  a  blood  test,  204 


244 


INDEX. 


H. 

Haematoidine,  225 

Hematuria',  203 

Hsenrin,  204 

Hsemoglobine,  204 

Hemoglobinuria,  203 

Hammorstein's  process  for  estimation  of 

globuline,  149 
Haycraft's  method  for  estimating  uric 

acid,  78 
Heller's  test  for  albumen,  124 

for  blood,  203 
Hemi-albumose,  154 

analysis  of,  154 

properties  of,  154 
Hippuric  acid,  83 

extraction  of,  84 

quantitative  analysis  of,  85 

physiology  and  pathology  of,  85 

tests  for,  84 
Hoppe-Seyler's  sugar  test,  166 
Huppert's*  reaction  (bile),  191 
Hydrobilirubine,  97 
Hydrogen-peroxide  in  urine,  116 
Hydroquinone,  96 
Hydruria,  29 

Hypobromite  method  for  urea  estima- 
tion, 57 
Hypoxanthine,  91 

I. 

Indican,  99 
Indigo  blue,  100 

red,  100 

sugar  test,  166 
Indirubine.   See  '  Urrhodine  '  and  'In- 
digo red.' 
Indol,  97 
Inosite,  178 

analysis  of,  178 

properties  of,  178 
Iodine  and  iodides,  elimination  of,  234 
Iodoform,  elimination  of,  235 
Iron,  elimination  of,  234 

J. 

Jaworowski's  test  for  albumen,  131 
K. 

Kairine,  elimination  of,  235 
Kidney,  circulation  of  blood  in,  13-15 

size  of,  2 

structure  of,  3-13 

weight  of,  2 

L. 

Lactic  acid,  187 
Lactose,  177 
Lecithine,  195 

Lechine's  reaction  (blood),  204 
Leucocytes  in  urine,  208 
Levulose,  177 

Lieben's  reaction  (acetone),  185 


Liebig's  urea  process,  53 
Lime,  estimation  of,  114 
Lipuria,  195 

Lithia  in  uric  acid  diathesis,  83 
M. 

Magnesia,  114 

triple  phosphate  of,  109 
Mechanism  of  urinary  secretion,  17-21 
Melanuria,  187 
Mercury,  elimination  of,  236 
Methsemog^obine,  206 
Micrococci^  urine,  84-214 
Milk  sugar K  177 

Millon's  reaction  (urea),  53,  153 
Moore's  test  for  sugar,  161 
Mucine,  150 

JVIurexide  reaction,  73-77 
Muscle  sugar,  178 

N. 

Naphthaline,  elimination  of,  236 
Naphthol  and  other  phenols,  elimination 

of,  236 

Neisser's  Gonococcus,  214 
Nitrates  and  nitrites  in  urine,  116 
Nitric  acid  test  for  albumen,  124 
Nitrogen,  total  elimination  of,  116 

O. 

Odour  of  urine,  25 

Orthonitrobenzaldehyde  reaction,  184 
Ost's  sugar  test,  163 
Oxalate  of  lime,  94 

analysis  of,  95 

calculi  of,  221 
Oxaluric  acid,  91 
Oxyhemoglobin  e,  206 
Oxyuris  vermicularis,  213 

P. 

Paracresol,  96 
Paraglobuline,  147 
Penicillium  glaucum,  175 
Peptones,  152 

analysis  of,  152 

properties  of,  152 
Peptonuria,  154 

Peroxide  of  hydrogen  in  urine,  116 
Pettenkofer's  bile  reaction,  193 
Phenic  acid,  96 

Phenyl-hydrazine  reaction,  167 

Phosphates,  107-113 

alkaline  and  earthy,  107 
qualitative  analysis  of,  110 
quantitative  analysis  of,  110 

Phosphatic  diathesis,  113 

Phosphaturia,  113 

Phosphogly eerie  acid,  110 

Phosphoric  acid,  107-110 
estimation  of,  110 

Picric  acid  test  for  albumen,  110 
for  sugar,  167 


INDEX. 


245 


Pigments,  biliary,  188 

urinary,  97 
Piperazine  in  uric  acid  diathesis,  83 
Pohl's  test  for  globuline,  149 
Polyuria,  29 

Potash,  estimation  of,  114 
Process  of  Bod eker.  (albumen),  139 

of  Brandberg  (albumen),  141 

of  Esbach  (albumen),  143 

of  Hammarstein  (albumen),  149 

of  Leconte  (urea),  51 

of  Liebig  (urea),  54 

of  Millon  (urea),  53 

of  Salkowski-Ludwig  (uric  acid),  79 

of  Tanretand  Troyes  (albumen),  138 
Propeptone,  154 

Prostatitis,  urethral  discharge  in,  211 

Ptomaines,  152 

Purdy's  sugar  estimation,  164 

Pus  in  urine,  208 

Day's  test  for,  209 
Pyrocatechin,  96 

Q. 

Quantity  of  urine  (normal\  28 
agencies  influencing  the,  29 

R. 

Reaction  of  Adamkievicz  (albumen),  132 

of  Agnotsti  (sugar),  167 

of  Almen  (sugar),  166 

of  Bayrac  (uric  acid),  79 

of  biuret  (peptones),  152,  153 

of  Bottger  (sugar),  165 

of  Chautard  (acetone),  184 

of  Dietrich  (uric  acid),  77 

of  Ehrlich  (bile),  192 

of  Fehling  (sugar),  163 

of  Gmelin  (bile),  190 

of  Hoppe -Seyler  (sugar),  166 

of  Lieben  (acetone),  183 

of  Millon  (urea,  albumen),  53,  121 

of  Moore-Heller  (sugar),  160 

of  Mulder  (sugar),  167 

of  murexide  (uric  acid),  73,  77 

of  Pettenkofer  (bile),  193 

of  Rosenberg  (uric  acid),  77 

of  Scherer  (inosite),  178 

of  Trommer  (bile),  162 

of  Worm-Muller,  160 

of  Zahsr,  145 
Residue,  solid,  of  urine,  31 
Rhubarb,  elimination  of,  239 
Rosaniline  test  for  acetone,  184 
Rosenbach's  bile  reaction,  191 

S. 

Saccharine,  elimination  of,  238 
Saccharomyces  of  urine,  214 
Safranin  sugar  test,  165 
Salicylates,  elimination  of,  237 
Salol,  elimination  of,  237 
Santonine,  elimination  of,  239 
Sarcine  or   ypoxan     ne,  91 


Sarcinse  urese,  214 
Schiff's  test  for  uric  acid,  77 
Schmiedeberg's  reaction,  165 
Secretion  of  urine,  theories  of,  17-21 
Sediments,  215 

of  bilirubine,  224 

of  carbonate  of  lime,  218 

of  cholesterine,  225 

of  cystine,  223 

of  hoematoidine,  225 

of  indigotine,  225 

non-organized,  216 

of  oxalate  of  lime,  221 

of  phosphate  of  lime,  223 

of  triple  phosphates,  222,  223 

of  tyrosine,  224 

of  urates,  219-221 

of  uroglaucine,  225 

of  xanthine,  224 
Serum  albumen,  120 
Silica  in  urine,  116 
Skatol,  97 

Soda,  estimation  of,  114 

in  urine,  113 
Sodium,  chloride  of,  103 
^Spectroscope,  206 
Spermatozoa,  199,  211 
Strongylus  gigas,  213 
Strontium,  elimination  of,  238 
Succinic  acid,  92 

as  an  albumen  test,  130 
Sugar  of  diabetes,  160 

of  milk,  177 

of  muscle,  178 

of  raisin,  176 

optical  analysis  of,  173 

pathological  significance  of,  173 

quantitative  analysis  of,  169-171 
Sulphates,  105 

Sulphuretted  hydrogen  in  urine,  203 
Sulphuric  acid,  105 

T. 

Tanret's  solution,  126 
Taurine,  192 

Temperature  of  urine,  28 
Thalline,  elimination  of,  239 
Toxicity  of  urine,  38 
Transitory  albuminuria,  155 
Transparency  of  urine,  24 
Trominer's  sugar  test,  162 
Tube  casts  in  urine,  198 
Turpentine,  elimination  of,  238 
Tyrosine,  ISO 

properties  of,  180 

sediments  of,  218 

tests  for,  181 

U. 

Uraemia,  68 

Urate,  acid  ammonium,  75 
acid  calcium,  75 
acid  magnesium,  75 
acid  sodium,  74 


246 


INDEX. 


Urate,  lithium,  76 
Urates,  74 

sediments  of,  218 
Urea,  43,  44 

artificial  production  of,  46 

chemistry  of,  46,  47 

modification  of  amount  of,  45 

nitrate  of.  48 

oxalate  of,  48 

physical  properties  of,  47 

preparation  of,  48 

quantitative  analysis  of,  41 
by  Leconte's  process,  51 
by  Liebig's  process,  53 
by  Yvon's  process,  58 
Ureometer  of  Doremus,  60 

of  Gerrard,  59 

of  Mercier,  62 

of  Noel,  61 

of  Regnard,  66 
Urethan,  elimination  of,  239 
Uric  acid  sediments,  221 
Urina  chyli,  25 

potus,  25 

sanguinis,  25 
Urine,  accidental  elements  of,  39 

colour  of,  25 

density  of,  28 

normal,  24 

transparency  of,  24 

toxicity  of,  38 


Urinometer,  31 
Urobiline,  97 
Urochrome,  99 
Uroerythrine,  99 
Uroglaucine,  100 
UrohsematoporphTrine,  98 
Uromelanine,  99 
Uropittine,  99 
Urrhodine,  100 

V. 

Volume  of  urine,  28 
in  health,  29 
in  disease,  30 


Weyl's  test  for  creatinine,  89 
X. 

Xanthine,  90 

calculi  of,  226 

sediments  of,  224 
Xanthogen  reaction,  231 
Xanthoproteic  reaction,  121 

Z. 

Zahor's  method  for  estimation  of  albu- 
men, 145 
Zeller's  test  for  melanine,  187 
Zouchlos's  albumen  test,  129 


ERRATA. 

Page  38,  line  15,  for  1  he  observed  '  read_ '  Bonchard  observed,'  etc. 
,,  145,    ,,     1,  for  '  Zohar '  read  1  Zahor.' 

,,  165,  second  line  from  bottom  of  page,  for  1  Bottiger '  read  1  Bottger.' 
,,  213,  ,,  ,,  ,,  ,,  ,,  for  'Ascaridis '  read  4  Ascaris.' 
,,  214,  line  8,  for  '  Bacillus  urinae  '  read  '  Bacillus  ureae.' 


THE  END. 


BAILLIERE,  TINDALL  AND  COX,  KING  WILLIAM  STREET,  STRAND. 


BY  THE  SAME  AUTHOR. 


 <X>>»<00  

Bright's  Disease.    London  :  J.  &  A.  Churchill.  Phila- 
delphia :  Lindsay  &  Blakiston. 

I  This  volume  comprises  a  series  of  six  lectures  on  Bright's  Disease 
of  the  Kidney,  delivered  at  the  Royal  Infirmary  of  Glasgow,  and 
afterwards  published  in  the  Medical  Press  and  Circular.  In  the 
present  form  they  have  been  revised  and  amplified,  and  cannot  fail  to 
be  acceptable  to  every  busy  practitioner  who  has  not  time  to  consult  a 
large  treatise.  The  subject  is  very  interestingly,  comprehensively,  and 
practically  treated.' — New  York  Medical  Record. 

I I  have  read  your  work  (Lectures  on  Bright's  Disease)  with  much 
pleasure,  and  consider  the  book  will  be  most  valuable  to  the  student. 
The  facts  are  put  very  lucidly,  and  the  reasoning  is  in  a  concise  form, 
showing  that  you  must  be  a  good  teacher  ;  and  T  hope  you  have,  or 
mean  to  obtain,  a  lectureship  in  some  good  school  of  medicine.' — 
George  Owen  Bees}  M.D.,  F.B.S.,  Senior  Consulting  Physician  to 
Guy's  Hospital. 


Observations  on  Therapeutics  and  Disease.  London: 
Churchill  &  Sons. 

'  Dr.  Black  is  one  of  those  thinkers  who  ought  to  be  encouraged.  .  .  . 
We  have  said  that  we  think  such  an  attempt  as  Dr.  Black's  is  one  to 
be  encouraged.  We  think  so  because  boldness  of  thought,  and  a  dis- 
position to  handle  the  problems  of  disease  and  of  health  in  a  large 
spirit,  are  very  necessary  to  that  great  reform  in  therapeutics  which 
we  all  hope  to  see.  There  is  much  ability  in  his  pamphlet,  and  it  will  be 
an  immense  gain  to  practical  medicine  if  he  succeeds  in  stirring  up  our 
scientific  therapeutists  to  look  at  questions  of  medication  in  a  broad 
way,  and  in  relation  to  the  great  physiological  states,  instead  of  merely 
ticketing  remedies  with  specific  titles,  and  inducing  the  hapless  practi- 
tioner to  discharge  them  at  a  supposed  peccant  organ,  as  a  boy  might 
aim  a  pea  from  a  pop-gun.' — Practitioner. 


(2),  ' 

*  Dr.  Black's  essay  displays  an  extensive  knowledge  of  his  subject, 
and  though  many  of  his  views  are  necessarily  open  to  controversy,  they 
are  well  worth  consideration.' — Brit,  and  For.  Med.-Chir.  Rev. 

'  The  book  shows  that  its  author  possesses  considerable  speculative 
ability,  and  that  he  entertains  a  healthy  hatred  of  everything  savour- 
ing of  refinement  in  diagnosis,  as  well  as  of  all  those  who,  in  the 
pursuit  of  new  remedies  and  theories,  neglect  to  exhaust  the  curative 
capacities  of  known  drugs.  ...  It  is  suggestive,  and  written  with 
considerable  vigour.' — Edin.  Med.  Jour. 

'  We  have  a  thoughtful  and  carefully  written  pamphlet  from  Dr. 
Black  on  "  Therapeutics  and  Disease."  .  .  .  There  is  a  great  deal  of 
hard  reading  in  his  pamphlet,  and  we  shall  not  attempt  to  do  justice 
to  the  author  in  tracing  his  observations  throughout.  His  endeavour 
is  to  indicate  certain  conditions  of  the  system  which  give,  as  it  were, 
distinct  opportunities  for  the  attack  of  diseases,  and  then  to  show 
how  remedies  which  will  cure  these  diseases  do  so  by  restoring  the 
system  to  its  properly  balanced  state.  We  are  compelled  to  place  Dr. 
Black's  classification  thus  vaguely,  for  there  is  too  much  in  it  to  analyze 
it  throughout.'— Chemist  and  Druggist. 

'  Your  "  Observations  on  Therapeutics  and  Disease  "  I  have  read 
with  much  pleasure.' — Sir  Wm.  S.  Savory,  F.R.S.,  Surgeon  and 
Lecturer  on  Surgery,  St.  Bartholomew's  Hospital,  London. 

1  There  is  no  doubt  that  such  an  effort  as  yours  will  end  in  that  con- 
summation so  devoutly  to  be  wished — the  putting  of  the  study  of  the 
physiological  action  of  remedies  on  a  more  rational  basis.' — T.  E. 
Thorpe,  Prof,  of  Chemistry,  Anderson's  University,  Glasgow. 

*  I  have  read,  and  re-read,  your  pamphlet,  and  find  it  excellent.' — 
J.  Hjaltelin,  M.D.,  Chevalier  of  the  Legion  of  Honour,  Knight  of  the 
Order  of  Dannebrog  ;  Chief  Physician,  Iceland. 


Urinary  and  Eeproductive  Organs.  Second  Edition. 
London  :  Churchill  &  Sons.  Philadelphia  :  Lindsay 
&  Blakiston. 

'This  volume- -the  expansion,  as  its  author  tells  us,  of  a  proposed 
article  for  the  British  Medical  Journal — is  evidently  written  by  a 
gentleman  of  considerable  practical  experience,  deep  thought,  and 
extensive  reading.  .  .  .  The  style  of  the  author  is^easy  and  agree- 
able. ...  On  the  whole,  his  work  is  a  valuable  contribution  to 
medical  science,  and  being  penned  in  that  spirit  of  unprejudiced 
philosophical  inquiry  which  should  always  guide  a  true  physician, 
admirably  embodies  the  spirit  of  its  opening  quotation  from  Professor 
Huxley.' — Philadelphia  Medical  Times. 

1  We  like  the  tone  of  the  book,  though  it  advocates  many  proposi- 
tions not  accepted  by  the  profession.    Even  these,  we  think,  will 


•     ;  (  3  )  .. 

provoke  discussion,  and  so  hasten  the  time  when  the  functional  .diseases 
of  the  male  shall  be.  as  carefully  studied  and  treated  as  those  of  the 
female.' — Michigan  Univ.  Jour. 

'  There  is  so  much  cleverness,  bonhomie,  and  frankness,  and  ap- 
parent honesty  of  purpose  and  distaste  for  quackery,  that  hostile 
criticism  is  disarmed.  ...  It  is  an  interesting,  original,  and  will 
probably  prove  a  useful  work.  With  Chapter  IV.  begins  the  real 
work  of  the  author,  on  The  Pathology  and  Treatment  of  Nocturnal 
Enuresis  and  Spermatic  Incontinence.  This  is  followed  by  a  well- 
reasoned  and  manly  discussion  of  the  unsavoury  subject.  The  practical 
observations  on  treatment  are  sensible.  The  book  is  nicely  got  up,  and 
the  Table  of  Contents  and  Index  are  admirably  arranged.' — Edin. 
Med.  Jour. 

4  Dr.  Black  deserves  all  praise  for  the  manliness,  heartiness,  honesty 
of  purpose,  and  scientific  zeal  with  which  he  has  treated  a  subject 
which  has  become  distasteful  from  its  associations,  which  has  been  too 
much  shunned  by  our  profession,  and  which  has  unfortunately  fallen 
almost  altogether  into  the  hands  of  charlatans.  .  .  .  Dr.  Black's  book 
contains  much  useful  information,  and  will  doubtless  prove  interesting 
to  many  readers.' — Birmingham  Medical  Review. 

c  This  is  an  important  work,  showing  extensive  research,  and  con- 
veying much  information.' — The  Doctor. 

4  There  are  some  points  in  reference  to  the  functional  disorders  of 
the  reproductive  system  that  are  continually  forcing  themselves  upon 
medical  men,  but  which  few  practitioners  care  to  investigate.  Some 
of  these  have  been  fully  discussed  in  this  and  other  medical  journals, 
but,  unfortunately,  such  topics  are  apt  to  be  neglected,  and  hence  fall 
into  the  hands  of  those  least  qualified  to  discuss  them.  We  have  had 
by  us  for  a  long  time  a  volume  by  Dr.  Campbell  Black,  in  which  the 
topics  we  have  alluded  to  are  freely  discussed,  and  which  is,  perhaps, 
the  best  work  of  reference  respecting  them  for  medical  men.' — Med. 
Press  and  Circular. 

'  There  is  a  large  amount  "of  useful  information  in  the  book.  The 
author  has  evidently  read  a  good  deal,  and  can  think  for  himself.  .  .  . 
The  work  seems  to  have  been  written  by  a  professional  man  for  profes- 
sional men,  not  by  a  charlatan  for  the  public.  On  the  whole,  we  are 
disposed  to  regard  the  book  as  a  good,  well-intentioned  one.' — Brit,  and 
For.  Med.-Chir.  Rev, 

*  I  have  read  your  very  valuable  work  with  the  greatest  pleasure 
and  profit.' — Professor  Louis  A.  Sayre,  New  York. 


mil 


